Comparative Performance of Several Flexible Docking Programs and Scoring Functions:  Enrichment Studies for a Diverse Set of Pharmaceutically Relevant Targets

Abstract

Virtual screening by molecular docking has become a widely used approach to lead discovery in the pharmaceutical industry when a high-resolution structure of the biological target of interest is available. The performance of three widely used docking programs (Glide, GOLD, and DOCK) for virtual database screening is studied when they are applied to the same protein target and ligand set. Comparisons of the docking programs and scoring functions using a large and diverse data set of pharmaceutically interesting targets and active compounds are carried out. We focus on the problem of docking and scoring flexible compounds which are sterically capable of docking into a rigid conformation of the receptor. The Glide XP methodology is shown to consistently yield enrichments superior to the two alternative methods, while GOLD outperforms DOCK on average. The study also shows that docking into multiple receptor structures can decrease the docking error in screening a diverse set of active compounds.

Comparison of Structure‐ and Ligand‐Based Virtual Screening Protocols Considering Hit List Complementarity and Enrichment Factors

“…[11][12][13][14][15][16][17][18][19] The recent literature covers several retrospective comparisons of different structure-or ligand-based virtual-screening tools. [11,12,[20][21][22][23][24][25][26][27][28] One study was performed in our group. We compared the relative performance of structure-and ligandbased virtual-screening methods for four biogenic amine-binding GPCRs.…”

Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor

“…anthrax | transition path calculation | molecular dynamics | drug discovery | inhibition of protein-protein association S tructure-based drug design is increasingly used and has impacted the development of many drugs (1)(2)(3). Identifying inhibitors by virtual screening involves multiple steps, and its success depends on several factors: the efficiency of ligand and receptor conformational sampling (4)(5)(6)(7)(8)(9)(10)(11), the quality of the scoring function (12,13), the choice of docking pocket, and finally, the availability of a relevant assay to test the virtual screening candidates.…”

Applying Computational Scoring Functions to Assess Biomolecular Interactions in Food Science: Applications to the Estrogen Receptors

“…This was proposed by Charifson [151] because the combination of diverse functions could potentially compensate for the weaknesses of individual functions, and thus yield better overall scoring. While other strategies such as post-docking minimization [93,152] or topological filtering [153] The consensus scoring model has been widely accepted [154][155][156], There are three types of consensus methods: 1) rank by "vote", where only conformations within the top x% are polled; 2) rank by rank, where the ranking from each function is averaged; and 3) rank by number, where the score value from each function is averaged.…”