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Novel paradigms for drug discovery: computational multitarget screening.
Title | Novel paradigms for drug discovery: computational multitarget screening. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Jenwitheesuk, E, Horst, JA, Rivas, KL, Van Voorhis, WC, Samudrala, R |
Journal | Trends Pharmacol Sci |
Volume | 29 |
Issue | 2 |
Pagination | 62-71 |
Date Published | 2008 Feb |
ISSN | 0165-6147 |
Keywords | Animals, Anti-HIV Agents, Antimalarials, Computational Biology, Computer Simulation, Drug Delivery Systems, Drug Design, HIV-1, Humans, Plasmodium falciparum |
Abstract | An established paradigm in current drug development is (i) to identify a single protein target whose inhibition is likely to result in the successful treatment of a disease of interest; (ii) to assay experimentally large libraries of small-molecule compounds in vitro and in vivo to identify promising inhibitors in model systems; and (iii) to determine whether the findings are extensible to humans. This complex process, which is largely based on trial and error, is risk-, time- and cost-intensive. Computational (virtual) screening of drug-like compounds simultaneously against the atomic structures of multiple protein targets, taking into account protein-inhibitor dynamics, might help to identify lead inhibitors more efficiently, particularly for complex drug-resistant diseases. Here we discuss the potential benefits of this approach, using HIV-1 and Plasmodium falciparum infections as examples. We propose a virtual drug discovery 'pipeline' that will not only identify lead inhibitors efficiently, but also help minimize side-effects and toxicity, thereby increasing the likelihood of successful therapies. |
DOI | 10.1016/j.tips.2007.11.007 |
Alternate Journal | Trends Pharmacol. Sci. |
PubMed ID | 18190973 |