Are induced fit protein conformational changes caused by ligand-binding predictable? A molecular dynamics investigation

© 2017 Wiley Periodicals, Inc.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 38(2017), 15 vom: 05. Juni, Seite 1229-1237
1. Verfasser: Gao, Cen (VerfasserIn)
Weitere Verfasser: Desaphy, Jeremy, Vieth, Michal
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article active site flexibility active site rearrangement apo-holo transition conformational changes conformational transition induced fit ligand binding molecular dynamics Ligands Proteins
Beschreibung
Zusammenfassung:© 2017 Wiley Periodicals, Inc.
In this work, the ability of molecular dynamics simulations (MD) to prospectively predict regions of ligand binding sites that could undergo induced fit effects was investigated. Conventional MD was run on 39 apo structures (no ligand), and the resulting trajectories were compared to a set of 147 holo X-ray structures (ligand-bound). It was observed from the simulations, in the absence of the ligands, that structures exhibiting large residue conformational changes indicated higher likelihood of induced fit effects. Nevertheless, the simulation results did not perform better than using the normalized crystallographic structural factors as predictors of active-site rigid residues (87% predictive power) and mobile residues (47% predictive power). While the simulations could not produce full active sites conformations similar to holo-like states, it was found that the simulations could reproduce bound state conformations of individual residues. These results suggest potential issues in the use of unligated simulation frames directly for drug design applications such as ligand docking, and an overall caution in the use of protein flexibility in docking protocols should be emphasized. © 2017 Wiley Periodicals, Inc
Beschreibung:Date Completed 17.05.2019
Date Revised 17.05.2019
published: Print-Electronic
Citation Status MEDLINE
ISSN:1096-987X
DOI:10.1002/jcc.24714