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Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
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.

References

  1. T. Jain, B. Jayaram, FEBS Letters 579, 6659-6666 (2005).
  2. S. A. Shaikh, B. Jayaram, J. Med. Chem. 50, 2240-2244 (2007).
  3. S. A. Shaikh, T. Jain, G. Sandhu, N. Latha, B. Jayaram, Current Pharmaceutical Design 13, 3454-3470 (2007).
  4. A. Gupta, A. Gandhimathi, P. Sharma, B. Jayaram, Protein and Peptide Letters 14, 632-646 (2007).
  5. T. Singh, D. Biswas, B. Jayaram, “An Automated Active Site Identifier”, Manuscript in preparation.
  6. G. Mukherjee, B. Jayaram, “A Rapid Identification of Hit Molecules for Target Proteins via Physico-Chemical Descriptors”, Manuscript in preparation.
  7. G. Mukherjee, N. Patra, P. Barua, B. Jayaram, Journal of Computational Chemistry, 32, 893-907 (2011).
  8. T. T. Chang, H. J. Huang, K. J. Lee, H. W. Yu, H. Y. Chen, F. J. Tsai, M. F. Sun, and C. Y. C. Chen, J Biomol Struct Dyn 28, 309-321 (2010).
  9. A. K. Kahlon, S. Roy, and A. Sharma, J Biomol Struct Dyn 28, 201-210 (2010).
  10. T. C. Ramalho, M. V. J. Rocha, E. F. F. da Cunha, L. C. A. Oliveira, and K. T. G. Carvalho, J Biomol Struct Dyn 28, 227-238 (2010).
  11. L. I. S. Hage-Melim, C. H. T. P. Silva, E. P. Semighini, C. A. Taft, and S. V. Sampaio, J Biomol Struct Dyn 27, 27-35 (2009).

Goutam Mukherjee
Tanya Singh
B. Jayaram*

Department of Chemistry
Supercomputing Facility for Bioinformatics and Computational Biology
IIT Delhi, Hauz Khas
New Delhi-110016, India

Ph: 91-11-2659 1505
Ph: 91-11-2659 6786
Fx: 91-11-2658 2037
goutam@scfbio-iitd.res.in
tanya@scfbio-iitd.res.in
bjayaram@chemistry.iitd.ac.in
www.scfbio-iitd.res.in