Authors: Shaikh, S. A.; Jain, T.; Sandhu, G.; Latha, N.; Jayaram, B.

Source: Current Pharmaceutical Design, Volume 13, Number 34, December 2007 , pp. 3454-3470(17)

Publisher: Bentham Science Publishers

Abstract:

The discovery of new pharmaceuticals via computer modeling is one of the key challenges in modern medicine. The advent of global networks of genomic, proteomic and metabolomic endeavors is ushering in an increasing number of novel and clinically important targets for screening. Computational methods are anticipated to play a pivotal role in exploiting the structural and functional information to understand specific molecular recognition events of the target macromolecule with candidate hits leading ultimately to the design of improved leads for the target. In this review, we sketch a system independent, comprehensive physicochemical pathway for lead molecule design focusing on the emerging in silico trends and techniques. We survey strategies for the generation of candidate molecules, docking them with the target and ranking them based on binding affinities. We present a molecular level treatment for distinguishing affinity from specificity of a ligand for a given target. We also discuss the significant aspects of drug absorption, distribution, metabolism, excretion and toxicity (ADMET) and highlight improved protocols required for higher quality and throughput of in silico methods employed at early stages of discovery. We present a realization of the various stages in the pathway proposed with select examples from the literature and from our own research to demonstrate the way in which an iterative process of computer design and validation can aid in developing potent leads. The review thus summarizes recent advances and presents a viewpoint on improvements envisioned in the years to come for automated computer aided lead molecule discovery.

Keywords: Computational drug discovery; in silico drug design; binding affinity; binding specificity; ADMET

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161207782794220

Affiliations: 1: Department of Chemistry & Supercomputing Facility for Bioinformatics & Computational Biology,Indian Institute of Technology, Hauz Khas, New Delhi-110016, India.

Publication date: 2007-12-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Shaikh, S. A. ;  Jain, T. ;  Sandhu, G. ;  Latha, N. ;  Jayaram, B.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers