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Inventi Impact - Molecular Modeling

Patent Watch

  • Identification of pharmacophores from co-crystals of spleen tyrosine kinase (SYK) and SYK ligands

    The invention comprises for methods of identifying pharmacophores based on the spleen tyrosine kinase (SYK) protein or fragment thereof. The invention further provides methods of identifying SYK inhibitors using pharmacophores that are identified from co-crystals of SYK and its ligands. Further, the invention comprises methods of inhibiting SYK comprising contacting the residues lining the binding site with an inhibitor compound identified from pharmacophores.

  • Matriptase, a serine protease and its applications

    The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.

  • System and method for modeling atomic structures

    A system and method of an atomic tile including an elemental symbol for a corresponding element and a dot representation of at least one valance electron of the corresponding element. The dot representation are proximate to corresponding edges of the octagonal shape.

  • Retinal derivatives and methods for the use thereof for the treatment of visual disorders

    Compositions of and methods for using synthetic retinal derivatives as retinoid replacements and opsin agonists are provided.

  • Nucleic acids encoding IL-13 binding agents

    Agents (e.g., antibodies and fragments thereof) that bind specifically to IL 13 and modulate the ability of IL-13 to interact with IL-13 receptors and signaling mediators are disclosed.

  • HYPOALLERGENIC MOLECULES

    The present invention relates to a hypoallergenic molecule consisting of Bet v Ia or an allergen having at least 40% identity to Bet v Ia comprising mutations of at least four amino acid residues in the region of amino acids 100 to 125 of Bet v Ia or its corresponding region of the allergen having at least 40% identity to Bet v Ia.

  • Methods to identify responsive patients

    The present invention provides methods and kits for improving the progression-free survival of a patient suffering from gastrointestinal cancer and for assessing the sensitivity or responsiveness of the patient to treatment comprising bevacizumab.

  • ANTI-CD33 ANTIBODIES AND METHODS FOR TREATMENT OF ACUTE MYELOID LEUKEMIA USING THE SAME

    The present invention relates to antibodies that bind CD33. More particularly, the invention relates to anti-CD33 antibodies, fragments and homologues of these antibodies, humanized and resurfaced versions of these antibodies, functional equivalents and improved versions of these antibodies, immunoconjugates and compositions comprising these antibodies, and the uses of same in diagnostic, research and therapeutic applications. The invention also relates to a polynucleotide encoding these antibodies, vectors comprising the polynucleotides, host cells transformed with polynucleotides and methods of producing these antibodies.

  • Ivermectin Antagonizes Ethanol Inhibition in P2X4 Receptors

    A method for reducing alcohol consumption in a subject includes a step of identifying a subject exhibiting at least one symptom of alcoholism and then administering a therapeutically effective amount of an Ivermectin analogue-containing composition to the subject. A method of screening Ivermectin analogues for reducing alcohol consumption is also provided.

  • METHOD FOR THE HUMANIZATION OF ANTIBODIES AND HUMANIZED ANTIBODIES THEREBY OBTAINED

    Method for the humanization of the VH and VL variable regions of an animal antibody of known sequence, humanized animal antibody obtainable according to the method, in particular anti-NGF and anti-TrkA humanized animal antibodies.

  • NOVEL ANTI-IGF-IR ANTIBODIES AND USES THEREOF

    The present invention relates to novel antibodies capable of binding specifically to the human insulin-like growth factor I receptor IGF-IR and/or capable of specifically inhibiting the tyrosine kinase activity of said IGF-IR receptor, especially monoclonal antibodies of murine, chimeric and humanized origin, as well as the amino acid and nucleic acid sequences coding for these antibodies. The invention likewise comprises the use of these antibodies as a medicament for the prophylactic and/or therapeutic treatment of cancers overexpressing IGF-IR or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the overexpression of the IGF-IR receptor. The invention finally comprises products and/or compositions comprising such antibodies in combination with anti-EGFR antibodies and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.

  • ANTIBODY VARIANTS

    Antibody variants of parent antibodies are disclosed which have one or more amino acids inserted in a hypervariable region of the parent antibody and a binding affinity for a target antigen which is at least about two fold stronger than the binding affinity of the parent antibody for the antigen.

  • Methods of treating diabetes using IL-1beta antibodies

    An IL-1.beta. binding molecule, in particular an antibody to human IL-1.beta., especially a human antibody to human IL-1.beta. is provided, wherein the CDRs of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-1 mediated disease or disorder, e.g. osteoarthritis, osteoporosis and other inflammatory arthritides.

  • Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin

    Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic; hyperproliferative, and/or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

  • HIGH THROUGHPUT ENSEMBLE-BASED DOCKING AND ELUCIDATION OF THREE-DIMENSIONAL STRUCTURAL CONFIRMATIONS OF FLEXIBLE BIOMOLECULAR TARGETS

    Methods for generating putative ligand structures capable of altering the activity of a target effector molecule comprise: constructing an elongated monomer of the target effector molecule; constructing a three dimensional model of the target effector molecule under the influence of elongation using empirical three dimensional data, the model including a conformation revealing the binding portion of the target effector molecule to a putative ligand structure; generating a plurality of computational models of the target effector molecule; filtering the plurality of computational models against the three dimensional model created experimentally using a reiterative simulation analysis algorithm operable to identify and select a plurality of computational models having a root-mean square deviation below a predetermined threshold when compared to the three dimensional model of the target effector molecule; screening a plurality of ligands to rank the binding strength of each ligand with the plurality of computational models selected and selecting one or more ligands based on the ranking.

  • Nucleotide and Amino Acid Sequences for Calmodulin Protein Methyltransferase

    The present invention provides nucleic acid and amino acid sequences for calmodulin protein methyltransferase. The present invention also provides diagnostic tools and methods of using the present invention to diagnose and treat diseases and conditions linked with calmodulin methyltransferase, as well as methylated calmodulin intermediates.

  • Polypeptides capable of binding to CD64 comprising one or more heterologous T cell epitopes and their uses

    The invention relates to the use of a polypeptide that comprises i) a first portion comprising the part of human Fc that binds to CD64, and ii) a second portion comprising one or more heterologous T cell epitopes for stimulating a cytotoxic T cell response. The polypeptide may be an antibody that may be used to stimulate a cytotoxic T cell response against pathogens and tumour cells in patients in need of such treatment.

  • SYSTEM AND METHOD FOR MODELLING A MOLECULE WITH A GRAPH

    Modelling a molecule by means of a graph, said graph comprising vertices and edges, each edge having a specific type, and said graph having cyclic orderings on the half-edges about at least one of the vertices, said system comprising means for determining the cyclic orderings on the half-edges about said at least one vertex by means of the spatial coordinates of the constituent atoms of the molecule, and means for determining the type of each edge of the graph by means of the relative spatial location of the constituent atoms of the molecule. Thereby automatic classification, comparison, specification, analysis and/or prediction of molecular structures can be provided because these molecular structures are represented by explicit combinatorial objects, and descriptors can be derived from the graph constructed in this manner. The descriptors are automatically computable from molecular databases, such as PDB or CATH, with no qualitative human intervention or subjective criteria. The invention can be applied to macromolecular structures such as proteins, protein globules, ligands, polymers, nucleotides, nucleic acids, RNA and DNA.

  • SYNTHETIC IMMUNOGLOBULIN DOMAINS WITH BINDING PROPERTIES ENGINEERED IN REGIONS OF THE MOLECULE DIFFERENT FROM THE COMPLEMENTARITY DETERMINING REGIONS

    Immunoglobulins which each have one or more amino acid modifications in at least one structural loop region of such immunoglobulins, where the modified loop region specifically binds to an epitope of an antigen to which an unmodified immunoglobulin does not significantly bind, obtained from display libraries.

  • COMPOUNDS AND METHODS FOR THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASE

    The present invention provides a method and composition for the treatment and prevention of an autoimmune disease such a multiple sclerosis which is mediated by autoreactive T cells. The administration of a NOD-1 agonist is shown to mediate an anti-inflammatory immune response. NOD-1 agonists suitable for use in the methods and compositions of the invention include diaminopimelic acid (DAP)-containing muropeptide compounds such as Tri-DAP and M-TriDAP.

  • COMPOSITION AND METHOD FOR TREATMENT OF REPERFUSION INJURY AND TISSUE DAMAGE

    The present invention provides compounds and methods for the treatment and prophylaxis of ischemia reperfusion injury. In particular the invention provides compounds which function to suppress Toll-like Receptor 2 biological function or expression.

  • MEX3C REGULATION AND TARGET TO CONTROL OBESITY AND DIABETES

    MEX3C deficiency impairs the development of white and brown adipose tissue. Hence the present invention provides, among other things, a method of screening a candidate compound for activity in inhibiting fat deposition in a subject in need thereof and/or treating a condition in a subject in need thereof, comprising: (a) contacting a candidate compound to a cell that expresses MEX3C protein; and then (b) detecting a quantity of expression of the MEX3C protein in the cell; a depression in the expression of MEX3C protein when the candidate compound is contacted thereto as compared to that expressed when the candidate compound is not contacted thereto indicating the compound is active in inhibiting fat deposition and/or treating a condition in a subject in need thereof. Methods of treatment and screening subjects are also described.

  • Compositions and methods for detecting and treating tumors containing acidic areas

    Improved compounds have been developed which are structured to be sequestered with very high specificity in acidic areas of tissues. When the compounds contain a radioisotope effective to report the presence of the compound the compounds are for detecting tumors containing hypoxic/acidic areas. When the compounds contain radioisotopes effective to kill cells the compounds are for treating tumors containing hypoxic/acidic areas. Methods for detecting and treating tumors with such compounds are also disclosed.

  • Sophorolipid Analog Compositions

    A composition of matter comprising sophorolipids as antimicrobial agents, antifungal agents, biopesticides, for uses as drugs to treat HIV, septic shock, cancer, asthma, dermatological conditions, as spermicidal agents, as anti-inflammatory drugs, as ingredients in cosmetics and building blocks for monomers and polymers and self-assembled templates for further chemical elaboration.

  • PEPTIDES USEFUL AS DUAL CASPASE-2/-6 INHIBITORS AND THEIR BIOLOGICAL APPLICATIONS

    The present disclosure relates to peptides having a core sequence as described herein as well as application of the disclosed technology as inhibitors of caspase-2 and/or -6 activity.

  • METHODS FOR TREATING IMMUNE THROMBOCYTOPENIA

    Polypeptides and other compounds that can bind specifically to the C.sub.H2-C.sub.H3 cleft of an immunoglobulin molecule, and methods for using such polypeptides and compounds to inhibit Fc-mediated immune complex formation in autoimmune/immune thrombocytopenia.

  • Glycoprotein Hormone Analogs

    This invention relates to the field of glycoprotein hormone analogs and their uses as agonists, antagonists, targeting vectors, and immunogens. In particular, this invention describes a method for stabilizing a heterodimer that permits the preparation of functional glycoprotein hormone analogs. The analogs of present invention comprise at least one alpha subunit polypeptide and at least one beta subunit polypeptide, wherein the seatbelt region of the beta subunit is linked to the alpha subunit. The invention also provides for a beta subunit polypeptide wherein the C-terminal amino acid is from residue 10 to residue 20 of the seatbelt region.

  • HETEROGENEOUS FOLDAMERS CONTAINING alpha, beta, and/or gamma-AMINO ACIDS

    Disclosed are isolated, unnatural polypeptides containing cyclically-constrained .beta.-amino acid residues and cyclically-constrained .gamma.-amino acid residues. The compounds are unnatural and because they contain rotationally constrained residues that are not amenable to enzymatic degradation, the compounds are useful to probe protein-protein and other large molecule interactions.

  • Crystal structure of human alpha-N-acetylglucosaminidase

    The present invention provides the three-dimensional structure of human .alpha.-N-acetylglucosaminidase (NAGLU) protein. This crystallographic information is useful in the identification and development of novel binding compounds of NAGLU, NAGLU mutants, for example, those associated with Sanfilippo syndrome type B (mucopolysaccharidosis III B (MPS III-B)), and other NAGLU family members (family 89 .alpha.-N-acetylglucosaminidase) which may modulate the activity and/or stability of mutated NAGLU. Such compounds may be useful for the treatment of Sanfilippo syndrome type B (mucopolysaccharidosis III B (MPS III-B)).

  • COMPLEMENT RECEPTOR 2 TARGETED COMPLEMENT MODULATORS

    Modulation of the complement system represents a therapeutic modality for numerous pathologic conditions associated with complement activation. In a strategy to prepare complement inhibitors that are targeted to sites of complement activation and disease, compositions comprising a complement inhibitor linked to complement receptor (CR) 2 are disclosed. The disclosed are compositions can be used in methods of treating pathogenic diseases and inflammatory conditions by modulating the complement system.

  • PROCESS FOR THE PRODUCTION OF ARACHIDONIC ACID AND/OR EICOSAPENTAENOIC ACID

    The present invention relates to a new process for the production of arachidonic acid and/or eicosapentaenoic acid in plants through the co-expression of a .DELTA.-12-/.DELTA.-15-desaturase, .DELTA.-9-elongase, .DELTA.-8-desaturase and a .DELTA.-5-desaturase and a process for the production of lipids or oils having an increased content of unsaturated fatty acids, in particular .omega.-3 and .omega.-6 fatty acids having at least two double bonds and a 18 or 20 carbon atom chain length. Preferably the arachidonic acid and eicosapentaenoic acid are produced in at least a 1:2 ratio. The invention furthermore relates to the production of a transgenic plants, preferably a transgenic crop plant, having an increased content of arachidonic acid and/or eicosapentaenoic acid, oils or lipids containing C.sub.18- or C.sub.20-fatty acids with a double bond in position 5, 8, 9, 11, 12, 14, 15 or 17 of the fatty acid produced, respectively due to the expression of the .DELTA.-12-/.DELTA.-15-desaturase, of the .DELTA.-9-elongase, of the .DELTA.-8-desaturase and of the .DELTA.-5-desaturase in the plant. The expression of the inventive .DELTA.-12-/.DELTA.-15-desaturase leads preferably to linoleic acid and linolenic acid as products having a double bond in the position 9, 12 and 15 of the fatty acid. The invention additionally relates to specific nucleic acid sequences encoding for proteins with .DELTA.-12-/.DELTA.-15-desaturase-, .DELTA.-9-elongase-, .DELTA.-8-desaturase- or .DELTA.-5-desaturase-activity, nucleic acid constructs, vectors and transgenic plants containing said nucleic acid sequences.

  • MODULATION OF ANXIETY THROUGH BLOCKADE OF ANANDAMIDE HYDROLYSIS

    Fatty acid amide hydrolase inhibitors of the Formula: ##STR00001## are provided wherein X is NH, CH.sub.2, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R.sub.1 and R.sub.2 are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R.sub.1 and R.sub.2 is absent, and that if Z is N, optionally R.sub.1 and R.sub.2 may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

  • TBC1D7 AS TUMOR MARKER AND THERAPEUTIC TARGET FOR CANCER

    The present invention relates to the roles played by the TBC1D7 genes in cancer, in particular, lung cancer or esophageal cancer, or carcinogenesis and features a method for treating and/or preventing cancer, in particular, lung cancer or esophageal cancer by administering a double-stranded molecule against one or more of the TBC1D7 genes or a composition, vector or cell containing such a double stranded molecule. The present invention also features methods for diagnosing lung or assessing/determining the prognosis of a patient with lung, especially NSCLC or SCLC, or esophageal cancer, using one or more over-expressed genes selected from among TBC1D7. To that end, TBC1D7 may serve as a novel biomarker for lung cancer or esophageal cancer. Also, disclosed are methods of identifying compounds for treating and preventing lung or esophageal cancer, using as an index for their effect on the over-expression of one or more of TBC1D7 in the lung cancer or esophageal cancer.

  • METHODS AND COMPOSITIONS TO INHIBIT EDEMA FACTOR AND ADENYLYL CYCLASE

    Small molecules and their derivatives are described for the treatment and/or prevention of intestinal fluid loss. Also disclosed are methods of using said molecules and their derivatives to treat and/or prevent conditions associated with increased levels of 3',5'-adenosine monophosphate. Specific compositions of the invention are also novel.

  • IMAGING METHOD

    A docking station for use in combined imaging of a tissue wound and a test substrate comprising a sample from a tissue wound, the docking station comprises means for connecting the station to a processor which processes and stores the images. The docking station also incorporates means for receiving a test substrate comprising a sample from a tissue wound. The docking station also includes means for docking a sensor in the station, which sensor detects the light reflected from an illuminated tissue wound, such that an image of the tissue wound can be communicated from the station to the processor. The means for docking is arranged such that when the sensor is docked in the station and the test substrate is received by the docking station, the sensor is positioned to detect the intensity of reflected light from the test substrate and communicates the detected intensity of reflected light to the processor to thus permit combined imaging of the tissue wound and test substrate. An apparatus for use in combined imaging of a tissue wound and a test substrate comprising a sample from a tissue wound, comprises such a dockingstation together with a sensor which detects the light reflected from a tissue wound and test substrate when illuminated and a test substrate for receiving a sample from a tissue wound. A method of imaging a wound comprises directing light over a wavelength range of less than 50 nm onto the wound (9). The light reflected from the wound (9) is detected with a sensor (5) that is sensitive to the intensity of the reflected light. The intensity of the reflected light is measured.

  • MALIGNANT PRECURSOR CELLS FROM DUCTAL CARCINOMA IN SITU LESIONS

    Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine.

  • USE OF COMPUTATIONALLY DERIVED PROTEIN STRUCTURES OF GENETIC POLYMORPHISMS IN PHARMACOGENOMICS FOR DRUG DESIGN AND CLINICAL APPLICATIONS

    Provided herein are computer-based methods for generating and using three-dimensional (3-D) structural models of target biomolecules. In particular, the target biomolecules are protein structural variants derived from genes containing genetic variations, or polymorphisms. The models are generated using molecular modeling techniques, such as homology modeling. The models can be used in structure-based drug design studies to identify drugs that bind to particular structural variants in structure-based drug design studies, for designing allele-specific drugs, population-specific drugs and for predicting clinical responses in patients. Molecular structure databases containing protein structural variant models also are provided.

  • AUTO-CONFIGURATION OF A DOCKED SYSTEM IN A MULTI-OS ENVIRONMENT

    A mobile computing device with a mobile operating system and desktop operating system running concurrently and independently on a shared kernel without virtualization. The mobile operating system provides a user experience for the mobile computing device that suits the mobile environment. The desktop operating system provides a full desktop user experience when the mobile computing device is docked to a secondary terminal environment. The mobile computing device configures the mobile operating system and/or the desktop operating system to take advantage of a docked secondary terminal environment. The mobile computing device may be a smartphone running the Android mobile OS and a full desktop Linux OS distribution on a modified Android kernel.

  • PREPARATION OF (R,R)-FENOTEROL AND (R,R)-OR (R,S)-FENOTEROL ANALOGUES AND THEIR USE IN TREATING CONGESTIVE HEART FAILURE

    This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogues which are highly effective at binding .beta.2-adrenergic receptors. Exemplary chemical structures for these analogues are provided. Also provided are pharmaceutical compositions including the disclosed (R,R)-fenoterol and fenoterol analogues, and methods of using such compounds and compositions for the treatment of cardiac disorders such as congestive heart failure and pulmonary disorders such as asthma or chronic obstructive pulmonary disease.

  • Compounds for the Inhibition of Herpes Viruses

    3D protein modeling and virtual screening of commercially-available compounds were performed to identify new inhibitors of the herpesvirus DNA polymerase, a key enzyme in the viral replication cycle. Two compounds (Nos 2 and 9) were particularly active against HSV-1 and HSV-2 strains and one compound (No 3) inhibited specifically cytomegalovirus (CMV) strains (overall hit rate of 25%). Some of the tested compounds inhibited wild-type viruses and strains resistant to current antiviral agents. New chemical entity derivatives of compound 2 with binding potential to the DNA polymerase retained an excellent activity against HSV-1, HSV-2 and VZV like the parental compound, as well against strains resistant to current antiviral agents. These non-nucleosidic herpesvirus DNA polymerase inhibitors with in vitro activity against drug-resistant clinical isolates warrant further pre-clinical studies.

  • NOVEL ANTI-CD38 ANTIBODIES FOR THE TREATMENT OF CANCER

    Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38.sup.+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

  • COMPOSITIONS AND METHODS FOR DETECTING OR ELIMINATING SENESCENT CELLS TO DIAGNOSE OR TREAT DISEASE

    Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.

  • COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS

    High throughput and virtual screening methods are disclosed that can identify potential anti-viral agents. The virtual screening methods identify agents that interact with a viral nucleoprotein binding site. The high throughput methods identify compounds that inhibit viral infection by binding to viral nucleoprotein. Also disclosed are pharmaceutical formulations useful for treating or preventing viral infections, especially influenza A.

  • THERAPEUTIC COMPOUNDS

    The invention relates to protein binding interacting/binding compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating 5-HT2C and/or RSK disorders, including diseases and disorders mediated by GPCRs and/or RSKs.

  • BACTERIAL SUPERANTIGEN VACCINES

    The present invention relates to genetically attenuated superantigen toxin vaccines altered such that superantigen attributes are absent, however the superantigen is effectively recognized and an appropriate immune response is produced. The attenuated superantigen toxins are shown to protect animals against challenge with wild type toxin. Methods of producing and using the altered superantigen toxins are described.

  • HUMAN MONOCLONAL ANTIBODIES TO CTLA-4

    In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

  • Neutralizing Antibodies And Methods Of Use Thereof

    This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the humanized monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.

  • ACE2 ACTIVATOR COMPOUNDS AND METHODS OF USE THEREOF

    The invention relates to methods of treating cardiovascular and cardiopulmonary diseases and associated conditions, including hypertension. The invention further relates to pharmaceutical compositions for treating cardiovascular and cardiopulmonary diseases, especially hypertension, and lung injury.

  • METHODS FOR IDENTIFYING AND USING MarR FAMILY POLYPEPTIDE BINDING COMPOUNDS

    Methods for identifying MarR family inhibiting compounds are described. The methods include the use of computer aided rational based drug design programs and three dimensional structures of MarR family polypeptides.

  • THREE-DIMENSIONAL STRUCTURES OF TALL-1 AND ITS COGNATE RECEPTORS AND MODIFIED PROTEINS AND METHODS RELATED THERETO

    Disclosed are TALL-1 and TALL-1 receptor protein homologues (agonists and antagonists) designed based on the three-dimensional structure of sTALL-1, eBCMA and eBAFF-R; agonist homologues of APRIL; methods of using wild-type APRIL to inhibit the activity of TALL-1; compositions comprising such homologues, nucleic acid molecules encoding such homologues, and therapeutic methods of using such compounds and compositions. Also disclosed are crystalline complexes of sTALL-1 and sTALL-1 in complex with either BCMA or BAFF-R; models of three-dimensional structures of such crystalline complexes and related structures, methods of drug design using any portion of such structures; methods of design and/or identification of regulatory peptides derived from the such structures; compounds identified by drug design using such structures; and the use of such compounds in therapeutic compositions and methods.

  • MOLECULAR PROPERTY MODELING USING RANKING

    Methods and articles of manufacture for modeling molecular properties using data regarding the partial orderings of compound properties, or by considering measurements of compound properties in terms of partial orderings are disclosed. One embodiment provides for constructing such partial orderings from data that is not already in an ordered form by processing training data to produce a partial ordering of the compounds with respect to a property of interest. Another embodiment of the invention may process the modified training data to construct a model that predicts the property of interest for arbitrary compounds.

  • ARTICLES OF MANUFACTURE AND METHODS FOR MODELING CHINESE HAMSTER OVARY (CHO) CELL METABOLISM

    The invention provides a Chinese Hamster Ovary (CHO) cell model and methods of using such a model. The invention provides methods and computer readable medium or media containing such models and methods.

  • Systems And Methods For Measuring And Modeling In Vivo Manganese Ion Transport In A Subject

    Described herein are systems and methods for quantitatively measuring manganese ion efflux in a subject. In general, the systems and methods compare imaging data from a subject taken over specific periods of time to pharmacokinetic models in order to measure manganese ion efflux rates from an organ in a subject. By understanding the specific location and rate of manganese ion efflux and influx from the organ, it is possible to more accurately correlate calcium ion activity. Calcium ion efflux is associated with a number of biological mechanisms in the subject, and the methods and systems described herein can be used as a diagnostic tool not only for monitoring calcium efflux in the subject but also aid in the treatment of diseases associated with changes in calcium ion efflux.

  • METHOD & APPARATUS FOR DOCKING A ROBOTIC DEVICE WITH A CHARGING STATION

    A docking system includes a mobile robotic device and a charging station to which the robotic device is to dock. The robotic device is comprised of sensors to capture a homing signal emitted by the charging station, docking logic that processes the homing signal so that it can be used to control the movements of the robotic device towards and dock with the charging station, and it is comprised of a mechanism for receiving a cylindrical charging post. The charging station is comprised of a circular platform in the center of which is located the charging post that is generally cylindrical in shape. The charging post includes a charging contact, ground contacts and an IR emitter. The geometry of the receiver mechanism elements and the shape of the charging post and geometry of the charging station generally permits the robotic device to approach the charging station and to dock with the charging station from any angle.

  • DOCKING STATION FOR ELECTRONIC DEVICE

    A docking station used for receiving an electronic device. The docking station includes a housing, a retractable docking port, and a rotating shaft. The housing defines a receiving groove. The docking port can be positioned by manipulation of the rotating shaft to be exposed in the receiving groove or retracted and hidden inside the housing.

  • Docking Station for Providing Digital Signage

    Various embodiments of digital signage systems and docking stations are described. In one embodiment, a digital signage system includes an electronic device having a rear surface and an opposing front surface at which a display of the electronic device may be viewed. The system also includes a body for supporting the electronic device. A recessed region is formed in the body from a top surface of the body, and the electronic device is positioned within the recessed region such that the rear surface of the electronic device fits entirely within the recessed region and the front surface of the electronic device is substantially flush with a portion of a top surface of the body that surrounds the recessed region. An aperture may be formed at least partially through the recessed region for receiving a cable assembly operable to connect to the electronic device. An elongated cutout may also be formed, extending from the aperture to an edge or edge surface of the body, and sized so that an insulated wire of the cable assembly can extend from the aperture to the edge or edge surface of the body.

  • DOCKING SYSTEM

    For each capture mechanism of a plurality of three capture mechanisms, a necked coupling element received by a corresponding socket slides therealong and engages a corresponding latch lever biased in an open position and rotates the latch lever to a closed position as the necked coupling element is slid within the socket towards a bottom thereof. A latch locked biased against the latch lever engages a notch in the latch lever when the latch lever is closed so as to latch the latch lever in the closed position and thereby capture the necked coupling element within the socket. The latch lever is unlatched by releasing the latch lock from engagement with the latch. Different latch levers incorporate different shaped surfaces that engage different corresponding necked coupling elements captured thereby so as to provide for respectively constraining in one, two and three degrees-of-freedom, respectively.

  • ADJUSTING OPHTHALMIC DOCKING SYSTEM

    An adjusting ophthalmic docking system is described that includes a curved contact element, disposed on a procedure eye, a conformation platform at a distal tip of an optical system to support an adjustment of the curved contact element, and a connector to accommodate the adjustment of the contact element. The curved contact element can be a meniscus-shaped contact lens, with a proximal surface radius larger than a distal surface radius. The contact lens can be made of an approximately refractive index-matching material, such as a fluoro-polymer.

  • System and Method of Providing Wireless Connectivity Between a Portable Computing Device and a Portable Computing Device Docking Station

    A portable computing device (PCD) docking station and method is disclosed. The PCD docking station may include an upper housing portion, a lower housing portion hingedly connected to the upper housing portion, a near field communication (NFC) transceiver connected to a battery and configured to energize the PCD docking station based upon communication with an NFC transceiver in a PCD, and a wireless dock connection configured to provide connectivity between the PCD and the PCD docking station. Further, the portable computing device may include a PCD pocket formed in the lower housing portion, the upper housing portion, or a combination thereof, wherein the PCD pocket is configured receive a PCD.

  • Universal Docking Station Compact

    A cosmetic compact that is capable of serving as a docking station for an assortment of power transfer, data transfer, and signal transfer connections. In general, power, data, and signal transfer connections will be of the input and output type, with respect to the compact. The compact docking station is able to provide power on an as needed basis or may be used to recharge one or more portable devices. A Universal Docking Station Compact according to the present invention is characterized by an assortment of power and data interfaces.

  • DOCKING STATION AND ELECTRONIC DEVICE

    According to one embodiment, a docking station includes: a first support; a second support; a second connector; a cover; and a second mark. The first support supports a second face of an electronic device so that a display screen of the electronic device is positioned in an inclined manner. The second support supports a side portion of the electronic device in the state. The second connector is exposed outward from an area positioned in the second support, and to be connectable to a first connector of the electronic device in the state. The cover covers at least a part of the first face in the state. The second mark is capable of being a guide corresponding to the first mark. The second mark guidably indicates to the operator to move the electronic device to a position at which the electronic device is connected while the display screen is inclined.

  • DOCKING STATION AND ELECTRONIC DEVICE

    A docking station includes a housing, and a connecting mechanism rotatably received in the housing. The connecting mechanism includes an interface. The connecting mechanism rotates from a first position exposed out of the housing to a second position hidden in the housing. When the connecting mechanism rotates to the first position, the interface is exposed out of the housing. When the connecting mechanism rotates to the second position, the interface is hidden in the housing.

  • DOCKING STATION

    The present invention relates to an improved docking station, which comprises a slide member, the top surface thereof is longitudinally formed with an accommodation slot allowing a connector plug to be positioned and to protrude, two opposite ends of the bottom of the accommodation slot are installed a pair of block sheets, a pair of fins are left/right extended from the slide member and a resilient unit is installed at the front; and a fasten member, a platform defined on the top surface thereof is installed with a slide groove having a width larger than the accommodation slot, the left and right lateral walls thereof are formed with a pair of rails for receiving the left and right fins, the inner wall of the front end of the fasten member is protrudingly formed with a positioning part, so the accommodation slot is enabled to elastically forward/backward slide with the slide member below the slide groove of the fasten member; so a connector socket at the bottom of a hand-held device having at least two different widths can be rapidly and conveniently inserted in the connector plug protruded from the slide member and the top surface of the fasten member, and the back board of each hand-held device is leaned against a base having the fasten member, for processing operations of charging or data transferring.

  • METHOD, APPARATUS AND COMPUTER PROGRAM PRODUCT FOR CREATING A WIRELESS DOCKING GROUP

    Method, apparatus, and computer program product embodiments are disclosed to enable simplified configuring of a wireless docking group for wireless devices by allowing a wireless device to communicate its capabilities and characteristics of one or more wireless devices within a wireless docking group, using a new Wireless Docking Protocol, to a wireless docking station that will use that information and the Wireless Docking Protocol to define an optimal set of connections for wireless devices in the wireless docking group.

  • METHOD, APPARATUS AND COMPUTER PROGRAM PRODUCT FOR CREATING A WIRELESS DOCKING GROUP

    Method, apparatus, and computer program product embodiments are disclosed to enable simplified configuring of a wireless docking group for wireless devices by allowing a wireless device to communicate its capabilities and characteristics of one or more wireless devices within a wireless docking group, using a new Wireless Docking Protocol, to a wireless docking station that will use that information and the Wireless Docking Protocol to define an optimal set of connections for wireless devices in the wireless docking group.

  • Docking Station

    A holder for an oblong-shaped device is provided. The holder can be a docking station for a media device and a keyboard. The holder can include a mounting tray and a mounting bracket assembly arranged on the mounting tray. The mounting bracket assembly can be configured such that the oblong-shaped device is securable to the mounting tray in both (i) a first position where a longitudinal axis of the oblong-shaped device extends substantially horizontally, and (ii) a second position where the longitudinal axis of the oblong-shaped device extends substantially vertically while the mounting tray is kept in a substantially upright position.

  • LADAR SENSOR FOR LANDING, DOCKING AND APPROACH

    A system for landing or docking a mobile platform is enabled by a flash LADAR sensor having an adaptive controller with Automatic Gain Control (AGC). Range gating in the LADAR sensor penetrates through diffuse reflectors. The LADAR sensor adapted for landing/approach comprises a system controller, pulsed laser transmitter, transmit optics, receive optics, a focal plane array of detectors, a readout integrated circuit, camera support electronics and image processor, an image analysis and bias calculation processor, and a detector array bias control circuit. The system is capable of developing a complete 3-D scene from a single point of view.

  • TRANSVERSE INSERTION TYPE NOTEBOOK COMPUTER DOCKING STATION

    A transverse insertion type notebook computer docking station for a notebook computer to be transversely inserted is provided. The transverse insertion type notebook computer docking station includes a body having a bottom surface, an inner side surface, a first side surface and a connecting port. The bottom surface, the inner side surface and the first side surface connect to each other, wherein normal directions of the bottom surface, the inner side surface and the first side surface are perpendicular to each other. The connecting port is disposed on the inner side surface. The transverse insertion type notebook computer docking station is used for a notebook computer to insert in, so as to prevent the notebook computer from toppling due to its own weight.

  • DEVICE FOR CONNECTING TWO APPARATUSES VIA AN ETHERNET LINK, AND DOCKING STATION FOR ONE OF SAID APPARATUSES

    A connection device for connecting a piece of master electronic equipment to a piece of peripheral electronic equipment, each being provided with a respective external connection port of a first type, the device comprising a master connection unit and a peripheral connection unit, each of which is provided with an external connection port of the first type for connecting to the corresponding piece of equipment, and which are connected to each other via electrical isolation using a link of a second type, namely of the Ethernet type, having a transmit line and a receive line, each unit including a first type/Ethernet interface connected to said lines and a power supply module mounted in common mode between the transmit and receive lines in order to transmit or receive AC over the link. A docking station for peripheral equipment including such a device.

  • HEAT PIPE DOCKING SYSTEM

    To provide electronic equipment having a heat discharging function capable of achieving the maximum in the signal processing capability of a portable terminal by preventing the functional restriction of the portable terminal by effectively discharging exothermic heat from the portable terminal at the time of coupling the portable terminal whose function is restricted by heat generation to an external device, as well as a heat discharging system and a heat discharging method.

  • HEAT PIPE DOCKING SYSTEM

    To provide electronic equipment having a heat discharging function capable of achieving the maximum in the signal processing capability of a portable terminal by preventing the functional restriction of the portable terminal by effectively discharging exothermic heat from the portable terminal at the time of coupling the portable terminal whose function is restricted by heat generation to an external device, as well as a heat discharging system and a heat discharging method.

  • APPARATUS FOR REMOVAL OF DOCKING PLATE IN SEMICONDUCTOR EQUIPMENT

    The present invention relates to an apparatus for removal of docking plate, wherein comprising a docking plate base device; and a handle removably joined to the docking plate base device and causing the docking plate base device to be removed from the semiconductor equipment when the handle is joined to the docking plate base device.

  • DRUG, DRUG GUIDANCE SYSTEM, MAGNETIC DETECTION SYSTEM, AND DRUG DESIGN METHOD

    It is intended to provide a drug delivery system which makes it possible to solve the existing technical problems and is easily usable in practice. A drug, which comprises an organic compound or an inorganic compound and has been magnetized by modifying a side chain and/or crosslinking side chains, is induced by a magnetic force into target tissues or an affected part.

  • DESIGN OF MOLECULES

    A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (O.sup.A.sub.1-n), where n is at least one; defining a population (P.sub.G=0) of at least one molecule; selecting an initial population (P.sub.parent) of at least one molecule (I.sub.1-I.sub.n) from the population (P.sub.G=0); and evaluating members (I.sub.1-I.sub.n) of the initial population (P.sub.parent) against at least one of the n achievement objectives (O.sup.A.sub.1-x), where x is from 1 to n.

  • MUTATIONAL PROFILE IN HIV-1 GAG CLEAVAGE SITE CORRELATED WITH PHENOTYPIC DRUG RESISTANCE

    The invention concerns novel mutations or mutational profiles of HIV-1 protease cleavage sites (CS) in the Gag region correlated with a phenotype causing alterations in sensitivity to anti-HIV drugs. The present invention also relates to the use of genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention further relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design and clinical management.

  • CRYSTAL OF HYPOXIA INDUCIBLE FACTOR 1 ALPHA PROLYL HYDROXYLASE

    The crystal structure of ligand-bound EGLN1 catalytic domain of prolyl hydroxylase is disclosed. These coordinates are useful in computer aided drug design for identifying compounds that regulate EGLN1 prolyl hydroxylase and thereby regulate HIF-regulated disorders.

  • PROTEINASE K INHIBITORS, METHODS AND COMPOSITIONS THEREFOR

    The synthesis, biological evaluation, and molecular modeling of alkoxysuccinyl-peptidyl-haloalkyl ketones for use as proteinase K inhibitors are described. Sample preparation processes for in situ RNA or DNA analysis using such inhibitors, methods and compositions therefor are provided.

  • DISEASE DIAGNOSIS AND TREATMENT USING COMPUTATIONAL MOLECULAR PHENOTYPING

    Disclosed are methods for detecting the presence or absence of disease in subjects based, at least in part, on results of analysis of a sample using computational molecular phenotyping. Further disclosed herein are methods for monitoring the status of subjects diagnosed with disease based at least partially on results of computational molecular phenotyping. The test samples disclosed herein are represented by, but not limited in anyway to, biopsy samples of body tissue.

  • DEVELOPMENT AND EVALUATION OF NOVEL CHINESE MATERIA MEDICA PREPARATIONS

    Nuclear receptor LXR is an important member of 49 nuclear receptors in human bodies and has irreplaceable regulatory effects on cholesterol and fat metabolisms. The regulation of the biological activity of LXR may have therapeutic effects to the conditions such as cardiovascular and cerebrovascular obstructions, non-insulin dependent hyperglycemia, immune function disorders, and central nerve functional degeneration. We have developed a group of novel Chinese materia medica preparations targeting nuclear receptor LXR by using a computer-simulated docking technology and a process for determining biological activities of human cells cultured ex vivo. The group of preparations are featured by simple ingredients, low costs, easy to prepare, etc. No significant adverse effects were found in initial acute toxicology analysis which was carried out using mice.

  • METHOD FOR INTEGRIN LIGAND DISCOVERY

    This invention relates generally to integrin ligand discovery and to a method of integrin ligand discovery base upon induction of ligand-induced epitopes. Such ligands have the potential to be active agent as anti-inflammatory, anti-angiogenesis and/or anti-thrombotic agents and for the treatment of integrin mediated diseases and/or conditions

  • SMALL MOLECULES FOR THE MODULATION OF MCL-1 AND METHODS OF MODULATING CELL DEATH, CELL DIVISION, CELL DIFFERENTIATION AND METHODS OF TREATING DISORDERS

    This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.

  • SMALL-MOLECULE INHIBITORS OF DENGUE AND WEST NILE VIRUS PROTEASES

    The present invention concerns methods and compositions involving small molecule inhibitors for the treatment or prophylaxis of flavivirus infection, such as dengue virus and West Nile virus.

  • METHOD OF MODELING FOR DRUG DESIGN, EVALUATION AND PRESCRIPTION IN THE TREATMENT OF DISEASE

    A method implemented on at least one specifically programmed computer to improve the outcome of a drug trial. The method includes (a) generating a parameterized mathematical model of disease and immune response, (b) including in the parameterized mathematical model effects from one or more drugs with time-dependent variables that can change during a therapy, (c) creating a calibrated model using empirical data to aid in determining parameters of the parameterized mathematical model, (d) determining responses of the calibrated model to a series of time-dependent drug therapies, and (e) selecting at least one therapy based on the determined responses of the model.

  • DISEASE DIAGNOSIS AND TREATMENT USING COMPUTATIONAL MOLECULAR PHENOTYPING

    Disclosed are methods for detecting the presence or absence of disease in subjects based, at least in part, on results of analysis of a sample using computational molecular phenotyping. Further disclosed herein are methods for monitoring the status of subjects diagnosed with disease based at least partially on results of computational molecular phenotyping. The test samples disclosed herein are represented by, but not limited in anyway to, biopsy samples of body tissue.

  • PROTEINASE K INHIBITORS, METHODS AND COMPOSITIONS THEREFOR

    The synthesis, biological evaluation, and molecular modeling of alkoxysuccinyl-peptidyl-haloalkyl ketones for use as proteinase K inhibitors are described. Sample preparation processes for in situ RNA or DNA analysis using such inhibitors, methods and compositions therefor are provided.

  • STRUCTURE-BASED FRAGMENT HOPPING FOR LEAD OPTIMIZATION AND IMPROVEMENT IN SYNTHETIC ACCESSIBILITY

    The invention develops a computer-aided drug design method and system to optimize a lead through structure-based drug design with synthetic accessibility. In this invention, two systems of the structure-based lead optimization are developed and implemented: 1) LeadOp ("short for lead optimization")--an algorithm that performs lead optimization through structure-based fragment hopping method; and 2) LeadOp+R (short for "lead optimization with synthetic accessibility based on chemical reaction route")--an algorithm that performs lead optimization with synthetic accessibility. LeadOp algorithm provides users to optimize a lead compound with various combinations of fragments with stronger binding based on group efficiency, generating lead with stronger potency. Furthermore, LeadOp+R provides an advantage in the selection of the new fragment to be assembled, which was identified based on the group efficiency calculated in the active site and reaction rule.

  • DESIGN AND USE OF NEW RECOMBINANT INTERFERONS WITH ALTERED SPATIAL CONFIGURATION AND THREE-DIMENSIONAL STRUCTURE

    This invention provides a crystalline recombinant interferon (rSIFN-co) having (i) the same amino acid sequence as that of human consensus interferon, and (ii) altered three-dimensional structure as compared to IFN-.alpha.2b. The interferon of the present invention exhibits enhanced biological activities. The present invention also provides a structure model of said interferon useful for drug screening and/or drug design and the mimetic of said interferon. The invention further provides methods of designing and using new recombinant interferons with altered spatial configuration and three-dimensional structure.

  • VIDEO TABLET AND DOCKING STATION AND METHOD OF USE

    A unit that includes a docking station and a tablet. The docking station includes a base having first and second docking recesses defined therein and docking station contacts positioned in at least the first docking recess. The tablet includes a housing having a video screen, a memory, at least one switch, and a power source positioned therein. The video screen, memory, at least one switch, and power source are in electrical communication and the housing includes first and second docking portions. At least the first docking portion includes tablet contacts thereon. The first and second docking portions of the tablet are positioned in the first and second docking recesses and the tablet contacts are in electrical communication with the docking station contacts. The tablet is removable from the docking station.

  • METHOD FOR PREDICTING AND MODELING ANTI-PSYCHOTIC ACTIVITY USING VIRTUAL SCREENING MODEL

    The present invention relates to the development of a virtual screening model for predicting antipsychotic activity using quantitative structure activity relationship (QSAR), molecular docking, oral bioavailability, ADME and Toxicity studies. The present invention also relates to the development of QSAR model using forward stepwise method of multiple linear regression with leave-one-out validation approach. QSAR model showed activity-descriptors relationship correlating measure (r.sup.2) 0.87 (87%) and predictive accuracy of 81% (rCV.sup.2=0.81). The present invention specifically showed strong binding affinity of the untested (unknown) novel compounds against anti-psychotic targets viz., Dopamine D2 and Serotonin (5HT.sub.2A) receptors through molecular docking approach. Theoretical results were in accord with the in vitro and in vivo experimental data. The present invention further showed compliance of Lipinski's rule of five for oral bioavailability and toxicity risk assessment for all the active Yohimbine derivatives. Therefore, use of developed virtual screening model will definitely facilitate the screening of more effective antipsychotic leads/drugs with improved antipsychotic activity and also reduced the drug discovery cost and duration.

  • VIDEO TABLET AND DOCKING STATION AND METHOD OF USE

    A unit that includes a docking station and a tablet. The docking station includes a base having first and second docking recesses defined therein and docking station contacts positioned in at least the first docking recess. The tablet includes a housing having a video screen, a memory, at least one switch, and a power source positioned therein. The video screen, memory, at least one switch, and power source are in electrical communication and the housing includes first and second docking portions. At least the first docking portion includes tablet contacts thereon. The first and second docking portions of the tablet are positioned in the first and second docking recesses and the tablet contacts are in electrical communication with the docking station contacts. The tablet is removable from the docking station.

  • METHOD FOR PREDICTING AND MODELING ANTI-PSYCHOTIC ACTIVITY USING VIRTUAL SCREENING MODEL

    The present invention relates to the development of a virtual screening model for predicting antipsychotic activity using quantitative structure activity relationship (QSAR), molecular docking, oral bioavailability, ADME and Toxicity studies. The present invention also relates to the development of QSAR model using forward stepwise method of multiple linear regression with leave-one-out validation approach. QSAR model showed activity-descriptors relationship correlating measure (r.sup.2) 0.87 (87%) and predictive accuracy of 81% (rCV.sup.2=0.81). The present invention specifically showed strong binding affinity of the untested (unknown) novel compounds against anti-psychotic targets viz., Dopamine D2 and Serotonin (5HT.sub.2A) receptors through molecular docking approach. Theoretical results were in accord with the in vitro and in vivo experimental data. The present invention further showed compliance of Lipinski's rule of five for oral bioavailability and toxicity risk assessment for all the active Yohimbine derivatives. Therefore, use of developed virtual screening model will definitely facilitate the screening of more effective antipsychotic leads/drugs with improved antipsychotic activity and also reduced the drug discovery cost and duration.

  • DESIGN OF MOLECULES

    A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (O.sup.A.sub.1-n), where n is at least one; defining a population (P.sub.G=0) of at least one molecule; selecting an initial population (P.sub.parent) of at least one molecule (I.sub.1-I.sub.n) from the population (P.sub.G=0); and evaluating members (I.sub.1-I.sub.n) of the initial population (P.sub.parent) against at least one of the n achievement objectives (O.sup.A.sub.1-x), where x is from 1 to n.

  • STRUCTURE-BASED FRAGMENT HOPPING FOR LEAD OPTIMIZATION AND IMPROVEMENT IN SYNTHETIC ACCESSIBILITY

    The invention develops a computer-aided drug design method and system to optimize a lead through structure-based drug design with synthetic accessibility. In this invention, two systems of the structure-based lead optimization are developed and implemented: 1) LeadOp ("short for lead optimization")--an algorithm that performs lead optimization through structure-based fragment hopping method; and 2) LeadOp+R (short for "lead optimization with synthetic accessibility based on chemical reaction route")--an algorithm that performs lead optimization with synthetic accessibility. LeadOp algorithm provides users to optimize a lead compound with various combinations of fragments with stronger binding based on group efficiency, generating lead with stronger potency. Furthermore, LeadOp+R provides an advantage in the selection of the new fragment to be assembled, which was identified based on the group efficiency calculated in the active site and reaction rule.

  • APPLICATION OF MULTIDIMENSIONAL MATRIX FOR DRUG MOLECULAS DESIGN AND THE METHODOLOGIES FOR DRUG MOLECULAR DESIGN

    The present invention relates to the application of multidimensional matrix for drug design and the methodology for drug design, which for the first time introduces the concept of matrix optimization in mathematics to the design of drugs and the relevant molecules. The present invention uses multidimensional matrix to analyze the permutation and combination of factors that affect the chemical structures and properties of drugs, and classifies and compares the huge amounts of factors need to be considered in the drug discovery according to certain features, thus utilizes fewer number of variables to represent the huge number of variable factors to specifically obtain chemical structures for effective drugs and improves the physicochemical properties of the compounds. By structural comparison of the results with the experimental data of known drugs or compounds in all stages of drug discovery, the present invention further optimizes the molecular chemical structure of drugs and significantly increases the specificity and efficiency of drug design, and significantly increases the efficiency of synthesis.

  • Structural Model Of G Protein-Coupled Receptor And Method For Designing Ligand Capable Of Binding To G Protein-Coupled Receptor Using The Structural Model

    The present invention provides a method for constructing a three-dimensional structural model of an activated intermediate of a G protein-coupled protein receptor (GPCR) or a complex between a GPCR and a ligand. The three-dimensional structural model may be used to identify, screen, search, evaluate, or design GPCR agonists or antagonists. In a representative embodiment, a three-dimensional structural model of a photoactivated intermediate of rhodopsin is constructed using molecule modeling software and structural coordinates of the crystal structure of rhodopsin. The three-dimensional structural model of rhodopsin is subsequently used to construct structural models of activated intermediates of other GPCRs.

  • SYSTEM AND METHODS FOR INTEGRATED AND PREDICTIVE ANALYSIS OF MOLECULAR, IMAGING, AND CLINICAL DATA FOR PATIENT-SPECIFIC MANAGEMENT OF DISEASES

    A system operating in a plurality of modes to provide an integrated analysis of molecular data, imaging data, and clinical data associated with a patient includes a multi-scale model, a molecular model, and a linking component. The multi-scale model is configured to generate one or more estimated multi-scale parameters based on the clinical data and the imaging data when the system operates in a first mode, and generate a model of organ functionality based on one or more inferred multi-scale parameters when the system operates in a second mode. The molecular model is configured to generate one or more first molecular findings based on a molecular network analysis of the molecular data, wherein the molecular model is constrained by the estimated parameters when the system operates in the first mode. The linking component, which is operably coupled to the multi-scale model and the molecular model, is configured to transfer the estimated multi-scale parameters from the multi-scale model to the molecular model when the system operates in the first mode, and generate, using a machine learning process, the inferred multi-scale parameters based on the molecular findings when the system operates in the second mode.