Enhanced conformational exploration of protein loops using a global parameterization of the backbone geometry

Bibliographische Detailangaben
Veröffentlicht in:	Journal of computational chemistry. - 1984. - 44(2023), 11 vom: 30. Apr., Seite 1094-1104
1. Verfasser:	O'Donnell, Timothée (VerfasserIn)
Weitere Verfasser:	Cazals, Frédéric
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2023
Zugriff auf das übergeordnete Werk:	Journal of computational chemistry
Schlagworte:	Journal Article Research Support, Non-U.S. Gov't Markov chain Monte Carlo high-dimensional sampling hit-and-run loop sampling protein flexibility tripeptide loop closure Proteins Amino Acids

Beschreibung
Zusammenfassung:	© 2023 Wiley Periodicals LLC. Flexible loops are paramount to protein functions, with action modes ranging from localized dynamics contributing to the free energy of the system, to large amplitude conformational changes accounting for the repositioning whole secondary structure elements or protein domains. However, generating diverse and low energy loops remains a difficult problem. This work introduces a novel paradigm to sample loop conformations, in the spirit of the hit-and-run (HAR) Markov chain Monte Carlo technique. The algorithm uses a decomposition of the loop into tripeptides, and a novel characterization of necessary conditions for Tripeptide Loop Closure to admit solutions. Denoting m the number of tripeptides, the algorithm works in an angular space of dimension 12 m. In this space, the hyper-surfaces associated with the aforementioned necessary conditions are used to run a HAR-like sampling technique. On classical loop cases up to 15 amino acids, our parameter free method compares favorably to previous work, generating more diverse conformational ensembles. We also report experiments on a 30 amino acids long loop, a size not processed in any previous work
Beschreibung:	Date Completed 24.03.2023 Date Revised 31.03.2023 published: Print-Electronic Citation Status MEDLINE
ISSN:	1096-987X
DOI:	10.1002/jcc.27067