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.
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
Combinatorial Chemistry & High Throughput Screening
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:
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.
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Cite this article as:
Ghemtio Leo, I. Perez-Nueno Violeta, Leroux Vincent, Asses Yasmine, Souchet Michel, Mavridis Lazaros, Maigret Bernard and W. Ritchie David, Recent Trends and Applications in 3D Virtual Screening, Combinatorial Chemistry & High Throughput Screening 2012; 15 (9) . https://dx.doi.org/10.2174/138620712803519707
DOI https://dx.doi.org/10.2174/138620712803519707 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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