Receptor flexibility is a critical issue in structure-based virtual screening methods. Although a multiple-receptor conformation docking is an efficient way to account for receptor flexibility, it is still too slow for large molecular libraries. It was reported that a fast ligand-centric, shape-based virtual screening was more consistent for hit enrichment than a typical single-receptor conform...

Existing flexible docking approaches model the ligand and receptor flexibility either separately or in a loosely coupled manner, which captures the conformational changes inefficiently. Here, we propose a flexible docking approach, MedusaDock, which models both ligand and receptor flexibility simultaneously with sets of discrete rotamers. We developed an algorithm to build the ligand rotamer li...

A major problem in structure-based virtual screening applications is the appropriate selection of a single or even multiple protein structures to be used in the virtual screening process. A priori it is unknown which protein structure(s) will perform best in a virtual screening experiment. We investigated the performance of ensemble docking, as a function of ensemble size, for eight targets of ...

The necessity of treating receptor flexibility in proteinligand docking has been widely acknowledged and is the subject of extensive research in the field of drug discovery [1]. The use of multiple discrete protein conformations, so-called ensemble docking, has been proven to be a valid concept to mimic target plasticity in docking experiments [2,3]. Using molecular dynamics (MD) the number of ...

This review will focus on the construction, refinement, and validation of G Protein-coupled receptor models for the purpose of structure-based virtual screening. Practical tips and tricks derived from concrete modeling and virtual screening exercises to overcome the problems and pitfalls associated with the different steps of the receptor modeling workflow will be presented. These examples will...