Benchmarking biomolecular force field-based Zn 2+ for mono- and bimetallic ligand binding sites.

Autor: Melse O; Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.; SynBiofoundry@TUM, Technical University of Munich, Straubing, Germany., Antes I; Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.; SynBiofoundry@TUM, Technical University of Munich, Straubing, Germany., Kaila VRI; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden., Zacharias M; Center for Functional Protein Assemblies (CPA), Technical University of Munich, Garching, Germany.
Jazyk: angličtina
Zdroj: Journal of computational chemistry [J Comput Chem] 2023 Mar 30; Vol. 44 (8), pp. 912-926. Date of Electronic Publication: 2022 Dec 09.
DOI: 10.1002/jcc.27052
Abstrakt: Zn 2+ is one of the most versatile biologically available metal ions, but accurate modeling of Zn 2+ -containing metalloproteins at the biomolecular force field level can be challenging. Since most Zn 2+ models are parameterized in bulk solvent, in-depth knowledge about their performance in a protein environment is limited. Thus, we systematically investigate here the behavior of non-polarizable Zn 2+ models for their ability to reproduce experimentally determined metal coordination and ligand binding in metalloproteins. The benchmarking is performed in challenging environments, including mono- (carbonic anhydrase II) and bimetallic (metallo-β-lactamase VIM-2) ligand binding sites. We identify key differences in the performance between the Zn 2+ models with regard to the preferred ligating atoms (charged/non-charged), attraction of water molecules, and the preferred coordination geometry. Based on these results, we suggest suitable simulation conditions for varying Zn 2+ site geometries that could guide the further development of biomolecular Zn 2+ models.
(© 2022 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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