Computer-Chemistry Center, Department of Chemistry and Pharmacy, Friedrich-Alexander-University Erlangen-Nürnberg, Nägelsbachstr. 25, 91052 Erlangen, Germany.
Computer-Chemistry Center, Department of Chemistry and Pharmacy, Friedrich-Alexander-University Erlangen-Nürnberg, Nägelsbachstr. 25, 91052 Erlangen, Germany.
Curr Opin Struct Biol. 2019 Apr;55:129-137. doi: 10.1016/j.sbi.2019.04.002. Epub 2019 May 14.
Recent developments in metadynamics simulation techniques for ligand binding to Class A GPCRs are described and the results obtained elucidated. The computational protocol makes good use of modern massively parallel hardware, making simulations of the binding/unbinding process routine. The simulations reveal unprecedented details of the ligand-binding pathways, including multiple binding sites in many cases. Free energies of binding are reproduced very well and the simulations allow prediction of the efficacy (agonist, antagonist etc.) of ligands.
描述了配体与 A 类 GPCR 结合的元动力学模拟技术的最新进展，并阐明了所获得的结果。该计算方案很好地利用了现代大规模并行硬件，使结合/解吸过程的模拟成为常规操作。这些模拟揭示了配体结合途径的前所未有的细节，包括在许多情况下存在多个结合位点。结合自由能得到了很好的再现，并且模拟允许预测配体的效力（激动剂、拮抗剂等）。
