Current Issue : July - September Volume : 2019 Issue Number : 3 Articles : 5 Articles
Multidrug efflux systems play a prominent role in medicine, as they are important\ncontributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major\nfacilitator superfamily that expels numerous drug compounds across the inner membrane of\nStaphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new\nopportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular\nmodeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over\n673 compounds from the PubChem database with a high (>80%) level of similarity to the chemical\nstructure of capsaicin was used to study the binding affinity of small molecule compounds for the\nNorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in\nparticular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of\nmajor facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy\ndescribed in this study, and the structural information of the potential novel inhibitors thus identified,\nwill stimulate others to pursue the development of better drugs to tackle multidrug resistance in\nS. aureus....
Although the branched capsular polysaccharides of Streptococcus agalactiae serotype III\n(GBSIII PS) and Streptococcus pneumoniae serotype 14 (Pn14 PS) differ only in the addition of a terminal\nsialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically\ndistinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide\na conformational rationale for the different antigenic epitopes identified for these PS.We find that\nside chains stabilize the proximal.........................
Proteins play crucial roles in the transportation and distribution of therapeutic substances,\nincluding metal ions in living systems. Some metal ions can strongly associate, while others show\nlow affinity towards proteins. Consequently, in the present work, the binding behaviors of..........................
Peptideâ??protein interactions are corner-stones of living functions involved in essential\nmechanisms, such as cell signaling. Given the difficulty of obtaining direct experimental structural\nbiology data, prediction of those interactions is of crucial interest for the rational development of\nnew drugs, notably to fight diseases, such as cancer or Alzheimerâ??s disease. Because of the high\nflexibility of natural unconstrained linear peptides, prediction of their binding mode in a protein\ncavity remains challenging. Several theoretical approaches have been developed in the last decade to\naddress this issue. Nevertheless, improvements are needed, such as the conformation prediction of\npeptide side-chains, which are dependent on peptide length and flexibility. Here, we present a novel\nin silico method, Iterative Residue Docking and Linking (IRDL), to efficiently predict peptideâ??protein\ninteractions. In order to reduce the conformational space, this innovative method splits peptides\ninto several short segments. Then, it uses the performance of intramolecular covalent docking to\nrebuild, sequentially, the complete peptide in the active site of its protein target. Once the peptide is\nconstructed, a rescoring step is applied in order to correctly rank all IRDL solutions. Applied on a set\nof 11 crystallized peptideâ??protein complexes, the IRDL method shows promising results, since it is\nable to retrieve experimental binding conformations with a Root Mean Square Deviation (RMSD) \nbelow 2 Angstrom in the top five ranked solutions. For some complexes, IRDL method outperforms two\nother docking protocols evaluated in this study. Hence, IRDL is a new tool that could be used in drug\ndesign projects to predict peptide-protein interactions....
In a previous work, we in silico annotated protein sequences of Citrus genus plants as\nputative tryptophan decarboxylase (pTDC). Here, we investigated the structural properties of Citrus\npTDCs by using the TDC sequence of Catharanthus roseus as an experimentally annotated reference\nto carry out comparative modeling and substrate docking analyses. The functional annotation as\nTDC was verified by combining 3D molecular modeling and docking simulations, evidencing the\npeculiarities and the structural similarities with C. roseus TDC. Docking with L-tryptophan as a ligand\nshowed specificity of pTDC for this substrate. These combined results confirm our previous in silico\nannotation of the examined protein sequences of Citrus as TDC and provide support for TDC activity\nin this plant genus....
Loading....