Proteochemometric modeling of HIV protease susceptibility

Background: A major obstacle in treatment of HIV is the ability of the virus to mutate rapidly into drug-resistant variants. A method for predicting the susceptibility of mutated HIV strains to antiviral agents would provide substantial clinical benefit as well as facilitate the development of new candidate drugs. Therefore, we used proteochemometrics to model the susceptibility of HIV to protease inhibitors in current use, utilizing descriptions of the physico-chemical properties of mutated HIV proteases and 3D structural property descriptions for the protease inhibitors. The descriptions were correlated to the susceptibility data of 828 unique HIV protease variants for seven protease inhibitors in current use; the data set comprised 4792 protease-inhibitor combinations. Results: The model provided excellent predictability (R2 = 0.92, Q2 = 0.87) and identified general and specific features of drug resistance. The model's predictive ability was verified by external prediction in ...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Maris Lapinsh, Martin Eklund, Ola Spjuth, Peteris Prusis, Jarl E. S. Wikberg
• Keywords: BMCBI 2008, HIV Protease, Protease, Protease Inhibitors