In the current era of high-throughput drug discovery and development,\r\nmolecular modeling has become an indispensable tool for identifying, optimizing and\r\nprioritizing small-molecule drug candidates. The required background in computational\r\nchemistry and the knowledge of how to handle the complex underlying protocols,\r\nhowever, might keep medicinal chemists from routinely using in silico technologies. Our\r\nobjective is to encourage those researchers to exploit existing modeling technologies more\r\nfrequently through easy-to-use graphical user interfaces. In this account, we present two\r\ninnovative tools (which we are prepared to share with academic institutions) facilitating\r\ncomputational tasks commonly utilized in drug discovery and development: (1) the\r\nVirtualDesignLab estimates the binding affinity of small molecules by simulating and\r\nquantifying their binding to the three-dimensional structure of a target protein; and (2) the\r\nMD Client launches molecular dynamics simulations aimed at exploring the\r\ntime-dependent stability of ligandââ?¬â??protein complexes and provides residue-based\r\ninteraction energies. This allows medicinal chemists to identify sites of potential\r\nimprovement in their candidate molecule. As a case study, we present the application of\r\nour tools towards the design of novel antagonists for the FimH adhesin.
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