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Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations

Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations
Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations
Many limitations of current computer-aided drug design arise from the difficulty of reliably predicting the binding affinity of a small molecule to a biological target. There is thus a strong interest in novel computational methodologies that claim predictions of greater accuracy than current scoring functions, and at a throughput compatible with the rapid pace of drug discovery in the pharmaceutical industry. Notably, computational methodologies firmly rooted in statistical thermodynamics have received particular attention in recent years. Yet free energy calculations can be daunting to learn for a novice user because of numerous technical issues and various approaches advocated by experts in the field. The purpose of this article is to provide an overview of the current capabilities of free energy calculations and to discuss the applicability of this technology to drug discovery
structure-based drug design, protein–ligand binding affinity, free energy calculations, molecular simulations
0920-654X
639-658
Michel, Julien
3dfda20a-a6fa-4214-8c7d-578f550b9ad7
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Michel, Julien
3dfda20a-a6fa-4214-8c7d-578f550b9ad7
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5

Michel, Julien and Essex, Jonathan W. (2010) Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations. Journal of Computer-Aided Molecular Design, 24 (8), 639-658. (doi:10.1007/s10822-010-9363-3). (PMID:20509041)

Record type: Article

Abstract

Many limitations of current computer-aided drug design arise from the difficulty of reliably predicting the binding affinity of a small molecule to a biological target. There is thus a strong interest in novel computational methodologies that claim predictions of greater accuracy than current scoring functions, and at a throughput compatible with the rapid pace of drug discovery in the pharmaceutical industry. Notably, computational methodologies firmly rooted in statistical thermodynamics have received particular attention in recent years. Yet free energy calculations can be daunting to learn for a novice user because of numerous technical issues and various approaches advocated by experts in the field. The purpose of this article is to provide an overview of the current capabilities of free energy calculations and to discuss the applicability of this technology to drug discovery

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More information

Published date: August 2010
Keywords: structure-based drug design, protein–ligand binding affinity, free energy calculations, molecular simulations

Identifiers

Local EPrints ID: 179883
URI: http://eprints.soton.ac.uk/id/eprint/179883
ISSN: 0920-654X
PURE UUID: c9b2c4c6-7853-4809-95a8-9e4a8e3f125b
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

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Date deposited: 04 Apr 2011 14:43
Last modified: 10 Dec 2019 01:55

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