Fast, metadynamics‐based method for prediction of the stereochemistry‐dependent relative free energies of ligand–receptor interactions. Issue 11 (24th February 2014)

• Record Type: Journal Article
• Authors: Plazinska, Anita; Plazinski, Wojciech; Jozwiak, Krzysztof
• Is Part Of: Journal of computational chemistry. Volume 35:Issue 11(2014)
• Page Start: 876
• Page End: 882
• Publication Date: 2014-02-24
• Subjects: Chemistry -- Data processing -- Periodicals; 542.85
• DOI: 10.1002/jcc.23563
• Languages: English
• ISSNs: 0192-8651

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The computational approach applicable for the molecular dynamics (MD)‐based techniques is proposed to predict the ligand–protein binding affinities dependent on the ligand stereochemistry. All possible stereoconfigurations are expressed in terms of one set of force‐field parameters [stereoconfiguration‐independent potential (SIP)], which allows for calculating all relative free energies by only single simulation. SIP can be used for studying diverse, stereoconfiguration‐dependent phenomena by means of various computational techniques of enhanced sampling. The method has been successfully tested on the β₂‐adrenergic receptor (β₂‐AR) binding the four fenoterol stereoisomers by both metadynamics simulations and replica‐exchange MD. Both the methods gave very similar results, fully confirming the presence of stereoselective effects in the fenoterol‐β₂‐AR interactions. However, the metadynamics‐based approach offered much better efficiency of sampling which allows for significant reduction of the unphysical region in SIP. © 2014 Wiley Periodicals, Inc.</p> </abstract>