Free Energy Computation for an Isomerizing Chromophore in a Molecular Cavity via the Average Solvent Electrostatic Configuration Model: Applications in Rhodopsin and Rhodopsin-Mimicking Systems

Author(s)

Nikolaev, Dmitrii M. ^[1] ; Manathunga, Madushanka ^[2] ; Orozco-Gonzalez, Yoelvis ^{[2, 3]} ; Shtyrov, Andrey A. ^[1] ; Guerrero Martinez, Yansel Omar ^[4] ; Gozem, Samer ^[3] ; Ryazantsev, Mikhail N. ; Coutinho, Kaline ^[4] ; Canuto, Sylvio ^[4] ; Olivucci, Massimo ^[2]

Affiliation

^[1] St Petersburg Acad Univ, Nanotechnol Res & Educ Ctr RAS, St Petersburg 194021 - Russia

^[2] Bowling Green State Univ, Dept Chem, Bowling Green, OH 43403 - USA

^[3] Georgia State Univ, Dept Chem, Atlanta, GA 30303 - USA

^[4] Univ Sao Paulo, Inst Fis, BR-05508090 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 17, n. 9, p. 5885-5895, SEP 14 2021.
• Web of Science Citations: 1

Abstract

We present a novel technique for computing the free energy differences between two chromophore ``isomers{''} hosted in a molecular environment (a generalized solvent). Such an environment may range from a relatively rigid protein cavity to a flexible solvent environment. The technique is characterized by the application of the previously reported ``average electrostatic solvent configuration{''} method, and it is based on the idea of using the free energy perturbation theory along with a chromophore annihilation procedure in thermodynamic cycle calculations. The method is benchmarked by computing the ground-state room-temperature relative stabilities between (i) the cis and trans isomers of prototypal animal and microbial rhodopsins and (ii) the analogue isomers of a rhodopsin-like light-driven molecular switch in methanol. Furthermore, we show that the same technology can be used to estimate the activation free energy for the thermal isomerization of systems i-ii by replacing one isomer with a transition state. The results show that the computed relative stability and isomerization barrier magnitudes for the selected systems are in line with the available experimental observation in spite of their widely diverse complexity. (AU)

• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants