Structure-Based Virtual Ligand Screening: Recent Success Stories

Abstract

Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. In this review, we first introduce structure-based virtual ligand screening and briefly comment on compound collections and target preparations. We also provide the readers with a list of resources, from chemoinformatics packages to compound collections, which could be helpful to implement a structure-based virtual screening platform. Then we discuss seventeen recent success stories obtained with various receptor-based in silico methods, performed on experimental structures (X-ray crystallography, 12 cases) or homology models (5 cases) and concerning different target classes, from the design of catalytic site inhibitors to drug-like compounds impeding macromolecular interactions. In light of these results, some suggestions are made about areas that present opportunities for improvements.

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

“…Virtual screening has long been an appealing strategy for drug discovery, but has proven complicated for even classical enzyme active sites (Brewerton 2008;Zoete et al 2009;van Montfort and Workman 2009;Villoutreix et al 2009;Cross et al 2009). Computational simulations have aided the rationalization of experimentally determined structure-activity relationships and have guided subsequent medicinal chemistry, but successful de novo prediction is rare.…”

Challenges of Antibacterial Discovery

“…While most of the programs discussed and tabulated below come from screening efforts, SBDD should play more of a role in the future. Virtual ligand screening and a number of its successes in human health drug discovery are reviewed by Villoutreix et al (377). A highly relevant recent review by Simmons et al focuses on rational discovery of antibacterials by SBDD (341).…”

Accelerated computational discovery of high-performance materials for organic photovoltaics by means of cheminformatics

“…[81][82][83][84][85][86] This technique has focused intensely in the search for molecules to be experimentally screened as potential drugs, or as drug leads. 87 More recently, QSPR were employed in the study of certain molecules for an understanding of the fundamental processes of cellular and organismic biology. 88,89 In similar fashion to QSPR, quantitative structure-activity relationships (QSAR) are used to study the biological activity of such problems.…”