Title:Recent Trends and Applications in 3D Virtual Screening
VOLUME: 15 ISSUE: 9
Author(s):Leo Ghemtio, Violeta I. Perez-Nueno, Vincent Leroux, Yasmine Asses, Michel Souchet, Lazaros Mavridis, Bernard Maigret and David W. Ritchie
Affiliation:Universite de Lorraine and #INRIA Nancy Grand Est, LORIA–UMR 6503, Equipe-projet Orpailleur, Campus scientifique, BP 239, 54506 Vandoeuvre-les-Nancy Cedex, France.
Keywords:3D-QSAR, 3D shape matching, chemical libraries, chemical spaces, computer-aided drug design, conformational
flexibility, docking, knowledge-based drug design, ligand-based drug design, molecular dynamics, pharmacophores, structurebased drug design, virtual screening
Abstract:Virtual screening (VS) is becoming an increasingly important approach for identifying and selecting
biologically active molecules against specific pharmaceutically relevant targets. Compared to conventional high
throughput screening techniques, in silico screening is fast and inexpensive, and is increasing in popularity in early-stage
drug discovery endeavours. This paper reviews and discusses recent trends and developments in three-dimensional (3D)
receptor-based and ligand-based VS methodologies. First, we describe the concept of accessible chemical space and its
exploration. We then describe 3D structural ligand-based VS techniques, hybrid approaches, and new approaches to
exploit additional knowledge that can now be found in large chemogenomic databases. We also briefly discuss some
potential issues relating to pharmacokinetics, toxicity profiling, target identification and validation, inverse docking,
scaffold-hopping and drug re-purposing. We propose that the best way to advance the state of the art in 3D VS is to
integrate complementary strategies in a single drug discovery pipeline, rather than to focus only on theoretical or
computational improvements of individual techniques. Two recent 3D VS case studies concerning the LXR-β receptor
and the CCR5/CXCR4 HIV co-receptors are presented as examples which implement some of the complementary
methods and strategies that are reviewed here.
