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Protein structure-based drug design: from docking to molecular dynamics


Śledź, Pawel; Caflisch, Amedeo (2017). Protein structure-based drug design: from docking to molecular dynamics. Current Opinion in Structural Biology, 48:93-102.

Abstract

Recent years have witnessed rapid developments of computer-aided drug design methods, which have reached accuracy that allows their routine practical applications in drug discovery campaigns. Protein structure-based methods are useful for the prediction of binding modes of small molecules and their relative affinity. The high-throughput docking of up to 106 small molecules followed by scoring based on implicit-solvent force field can robustly identify micromolar binders using a rigid protein target. Molecular dynamics with explicit solvent is a low-throughput technique for the characterization of flexible binding sites and accurate evaluation of binding pathways, kinetics, and thermodynamics. In this review we highlight recent advancements in applications of ligand docking tools and molecular dynamics simulations to ligand identification and optimization.

Abstract

Recent years have witnessed rapid developments of computer-aided drug design methods, which have reached accuracy that allows their routine practical applications in drug discovery campaigns. Protein structure-based methods are useful for the prediction of binding modes of small molecules and their relative affinity. The high-throughput docking of up to 106 small molecules followed by scoring based on implicit-solvent force field can robustly identify micromolar binders using a rigid protein target. Molecular dynamics with explicit solvent is a low-throughput technique for the characterization of flexible binding sites and accurate evaluation of binding pathways, kinetics, and thermodynamics. In this review we highlight recent advancements in applications of ligand docking tools and molecular dynamics simulations to ligand identification and optimization.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:14 November 2017
Deposited On:05 Dec 2017 15:03
Last Modified:19 Aug 2018 11:39
Publisher:Elsevier
ISSN:0959-440X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.sbi.2017.10.010
PubMed ID:29149726
Project Information:
  • : FunderSNSF
  • : Grant ID315230_149897
  • : Project TitleComputational studies of ligand binding and allostery
  • : FunderSNSF
  • : Grant ID31003A_169007
  • : Project TitleAnalysis of protein simulations and neural activity data

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