The recent application of 3D-QSAR and docking studies to novel HIV-protease inhibitor drug discovery.

Despite the availability of FDA approved inhibitors of HIV protease, numerous efforts are still ongoing to achieve 'near-perfect' drugs devoid of characteristic adverse side effects, toxicities, and mutational resistance. While experimental methods have been plagued with huge consumption of time and resources, there has been an incessant shift towards the use of computational simulations in HIV protease inhibitor drug discovery. Herein, the authors review the numerous applications of 3D-QSAR modeling methods over recent years relative to the design of new HIV protease inhibitors from a series of experimentally derived compounds. Also, the augmentative contributions of molecular docking are discussed. Efforts to optimize 3D QSAR and molecular docking for HIV-1 drug discovery are ongoing, which could further incorporate inhibitor motions at the active site using molecular dynamics parameters. Also, highly predictive machine learning algorithms such as random forest, K-means, decision trees, linear regression, hierarchical clustering, and Bayesian classifiers could be employed.