Paper Citing NAMD - Abstract
Garg, Rajni; Bhhatarai, Barun
QSAR and molecular modeling studies of HIV protease inhibitors
QSAR AND MOLECULAR MODELING STUDIES IN HETEROCYCLIC DRUGS I, 3:181-271, 2006
Acquired immunodeficiency syndrome (AIDS) and its related disorders, caused by retrovirus human immunodeficiency virus (HIV) are a major health concern worldwide. HIV protease is one of the major viral targets for the development of new chemotherapeutics. Currently, many HIV protease inhibitors are used in combination with HIV reverse transcriptase inhibitors. However, the use of current drugs regimens has several shortcomings, such as adherence, tolerability, long-term toxicity and drug- and cross-resistance. HIV is also known to have several mutants. Therefore, the development of new inhibitors that are less toxic, more tolerable, convenient and active against drug-resistant viruses is highly desirable. Several in-silico techniques are utilized in the process of drug design and development. One such technique is quantitative structure-activity relationship (QSAR). QSAR models reveal significant correlations between the biological activity and physico-chemical parameters and molecular descriptors. QSAR model can stand alone, support other approaches or be examined in tandem with equations of a similar mechanism to truly reveal its power. This work is devoted to a discussion of QSAR and molecular modeling studies especially those pertaining to 3D-QSAR on HIV protease inhibitors. It provides an overview of new ideas and their applications as they appear in the recent literature. Examples are given of peptidic and non-peptidic protease inhibitors. The role of hydrophobic, steric and electronic interactions in the design of HIV protease inhibitors is discussed. Linking a non-peptidic moiety to a peptidic backbone may provide a way of highlighting regions of interest. Some studies on such hybrid inhibitors are also discussed. Finally, studies on mutant protease data are included as they appear to be of utmost importance.
