Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
SANJEEVINI-A Lead Molecule Design Software
The ability of macromolecules to bind to their substrates in a highly specific manner is an important feature in many biological processes. The challenge for computer aided drug discovery is to achieve this specificity - with small molecule inhibitors - in binding to their biomolecular targets, at reduced cost and time while ensuring synthesizability, novelty of the scaffolds and proper ADMET profiles. Sanjeevini is a drug design software suite (1-7) developed to provide a computational pathway for automating lead molecule design. A sample of the various current approaches to drug design can be found in many of the recent articles published in this Journal, for example references 8-11.Our methodology treats macromolecular target and the lead compound at the atomic level and solvent as a dielectric continuum. It comprises several modules for diverse functionalities such as automated identification of potential binding sites (active sites) for the ligands (5), a rapid screening for identifying good candidates for any target protein from a million molecule database (6), optimization of their geometries and determination of partial atomic charges using quantum chemical / in-house methods (7), docking the candidates in the active site of target via Monte Carlo methods (4-5), estimating binding free energies through empirical scoring functions (1-2), followed by rigorous analyses of the structure and energetics of binding for further lead optimization. Each module is individually validated on a large data set of protein-ligand and DNA-ligand complexes with known structures and binding affinities. The Sanjeevini software is freely accessible at http://www.scfbio-iitd.res.in/sanjeevini/sanjeevini.jsp.
Department of Chemistry