An Average Solvent Electrostatic Configuration Protocol for QM/MM Free Energy Optimization: Implementation and Application to Rhodopsin Systems.

Autor:	Orozco-Gonzalez Y; Université de Strasbourg-CNRS, UMR 7504, Institut de Physique et Chimie des Mateŕiaux de Strasbourg , F-67034 Strasbourg, France.; USIAS Institut d'É;tudes Avanceés, Université de Strasbourg , 5 alleé du Geńeŕal Rouvillois, F-67083 Strasbourg, France.; Department of Chemistry, Bowling Green State University , Bowling Green, Ohio 43403, United States., Manathunga M; Department of Chemistry, Bowling Green State University , Bowling Green, Ohio 43403, United States., Marín MDC; Department of Biotechnology, Chemistry e Pharmacy, Università di Siena , via A. Moro 2, I-53100 Siena, Italy., Agathangelou D; Université de Strasbourg-CNRS, UMR 7504, Institut de Physique et Chimie des Mateŕiaux de Strasbourg , F-67034 Strasbourg, France., Jung KH; Department of Life Science and Institute of Biological Interfaces, Sogang University 35 Baekbeom-Ro , Mapo-Gu, Seoul 04107, Korea., Melaccio F; Department of Biotechnology, Chemistry e Pharmacy, Università di Siena , via A. Moro 2, I-53100 Siena, Italy., Ferré N; Aix-Marseille Univ, CNRS, ICR , 13013 Marseille, France., Haacke S; Université de Strasbourg-CNRS, UMR 7504, Institut de Physique et Chimie des Mateŕiaux de Strasbourg , F-67034 Strasbourg, France., Coutinho K; Instituto de Física, Universidade de São Paulo , 05508-090 Cidade Universitária, São Paulo/SP, Brazil., Canuto S; Instituto de Física, Universidade de São Paulo , 05508-090 Cidade Universitária, São Paulo/SP, Brazil., Olivucci M; Université de Strasbourg-CNRS, UMR 7504, Institut de Physique et Chimie des Mateŕiaux de Strasbourg , F-67034 Strasbourg, France.; USIAS Institut d'É;tudes Avanceés, Université de Strasbourg , 5 alleé du Geńeŕal Rouvillois, F-67083 Strasbourg, France.; Department of Chemistry, Bowling Green State University , Bowling Green, Ohio 43403, United States.; Department of Biotechnology, Chemistry e Pharmacy, Università di Siena , via A. Moro 2, I-53100 Siena, Italy.
Jazyk:	angličtina
Zdroj:	Journal of chemical theory and computation [J Chem Theory Comput] 2017 Dec 12; Vol. 13 (12), pp. 6391-6404. Date of Electronic Publication: 2017 Nov 21.
DOI:	10.1021/acs.jctc.7b00860
Abstrakt:	A novel atomistic methodology to perform free energy geometry optimization of a retinal chromophore covalently bound to any rhodopsin-like protein cavity is presented and benchmarked by computing the absorption maxima wavelengths (λ max ) of distant rhodopsin systems. The optimization is achieved by computing the Nagaoka's Free Energy Gradient (FEG) within an Average Solvent Electrostatic Configuration (ASEC) atomistic representation of the thermodynamic equilibrium and minimizing such quantity via an iterative procedure based on sequential classical MD and constrained QM/MM geometry optimization steps. The performance of such an ASEC-FEG protocol is assessed at the CASPT2//CASSCF/Amber level by reproducing the λ max values observed for 12 mutants of redesigned human cellular retinol binding protein II (hCRBPII) systems; a set of 10 distant wild-type rhodopsins from vertebrates, invertebrates, eubacteria, and archaea organisms; and finally a set of 10 rhodopsin mutants from an eubacterial rhodopsin. The results clearly show that the proposed protocol, which can be easily extended to any protein incorporating a covalently bound ligand, yields correct λ max trends with limited absolute errors.
Databáze:	MEDLINE
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