Current trends in computer aided drug design and a highlight of drugs discovered via computational techniques: A review

Abstract

Computer-aided drug design (CADD) is one of the pivotal approaches to contemporary pre-clinical drug discovery, and various computational techniques and software programs are typically used in combination, in a bid to achieve the desired outcome. Several approved drugs have been developed with the aid of CADD. On SciFinder®, we evaluated more than 600 publications through systematic searching and refining, using the terms, virtual screening; software methods; computational studies and publication year, in order to obtain data concerning particular aspects of CADD. The primary focus of this review was on the databases screened, virtual screening and/or molecular docking software program used. Furthermore, we evaluated the studies that subsequently performed molecular dynamics (MD) simulations and we reviewed the software programs applied, the application of density functional theory (DFT) calculations and experimental assays. To represent the latest trends, the most recent data obtained was between 2015 and 2020, consequently the most frequently employed techniques and software programs were recorded. Among these, the ZINC database was the most widely preferred with an average use of 31.2%. Structure-based virtual screening (SBVS) was the most prominently used type of virtual screening and it accounted for an average of 57.6%, with AutoDock being the preferred virtual screening/molecular docking program with 41.8% usage. Following the screening process, 38.5% of the studies performed MD simulations to complement the virtual screening and GROMACS with 39.3% usage, was the popular MD software program. Among the computational techniques, DFT was the least applied whereby it only accounts for 0.02% average use. An average of 36.5% of the studies included reports on experimental evaluations following virtual screening. Ultimately, since the inception and application of CADD in pre-clinical drug discovery, more than 70 approved drugs have been discovered, and this number is steadily increasing over time.

Keywords: Computational studies; Computer-aided drug design; Software programs; Virtual screening.