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

Author(s):Show less -

Orozco-Gonzalez, Yoelvis ^{[1, 2, 3]} ; Manathunga, Madushanka ^[3] ; Marin, Maria del Carmen ^[4] ; Agathangelou, Damianos ^[1] ; Jung, Kwang-Hwan ^{[5, 6]} ; Melaccio, Federico ^[4] ; Ferre, Nicolas ^[7] ; Haacke, Stefan ^[1] ; Coutinho, Kaline ^[8] ; Canuto, Sylvio ^[8] ; Olivucci, Massimo ^{[1, 2, 3, 4]}

Affiliation

^[1] Univ Strasbourg, CNRS, UMR 7504, Inst Phys & Chim Mat Strasbourg, F-67034 Strasbourg - France

^[2] Univ Strasbourg, USIAS Inst Etudes Avancees, 5 Allee Gen Rouvillois, F-67083 Strasbourg - France

^[3] Bowling Green State Univ, Dept Chem, Bowling Green, OH 43403 - USA

^[4] Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena - Italy

^[5] Sogang Univ, Dept Life Sci, 35 Baekbeom Ro, Seoul 04107 - South Korea

^[6] Sogang Univ, Inst Biol Interfaces, 35 Baekbeom Ro, Seoul 04107 - South Korea

^[7] Aix Marseille Univ, CNRS, ICR, F-13013 Marseille - France

^[8] Univ Sao Paulo, Inst Fis, Cidade Univ, BR-05508090 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 13, n. 12, p. 6391-6404, DEC 2017.
• Web of Science Citations: 8

Abstract

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 (lambda(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 lambda(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 lambda(max) trends with limited absolute errors. (AU)

• FAPESP's process: 13/11634-0 - Search for fluorescent Rhodopsins with multiconfigurational quantum chemistry based QM/MM models
• Grantee: Yoelvis Orozco González
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 12/15161-7 - Solvent effect on excited electronic states dynamics and on nonradioactive deactivation mechanisms
• Grantee: Yoelvis Orozco González
• Support Opportunities: Scholarships in Brazil - Post-Doctoral