TY - JOUR

T1 - Free Energy Computation for an Isomerizing Chromophore in a Molecular Cavity via the Average Solvent Electrostatic Configuration Model. Application to Rhodopsin and Rhodopsin-mimicking Systems

AU - Николаев, Дмитрий Михайлович

AU - Manathunga, Madushanka

AU - Orozco-Gonzalez, Yoelvis

AU - Shtyrov, Andrey A

AU - Martínez, Yansel Omar Guerrero

AU - Gozem, Samer

AU - Ryazantsev, Mikhail N.

AU - Coutinho, Kaline

AU - Canuto, Sylvio

AU - Olivucci, Massimo

N1 - Dmitrii M. Nikolaev, Madushanka Manathunga, Yoelvis Orozco-Gonzalez, Andrey A. Shtyrov, Yansel Omar Guerrero Martínez, Samer Gozem, Mikhail N. Ryazantsev, Kaline Coutinho, Sylvio Canuto, and Massimo Olivucci. Journal of Chemical Theory and Computation 2021 17 (9), 5885-5895 DOI: 10.1021/acs.jctc.1c00221

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

UR - https://pubs.acs.org/doi/10.1021/acs.jctc.1c00221

UR - https://proxy.library.spbu.ru:2136/doi/10.1021/acs.jctc.1c00221

M3 - Article

VL - 17

SP - 5885

EP - 5895

JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

SN - 1549-9618

IS - 9

ER -