TY - JOUR

T1 - Free Energy Computation for an Isomerizing Chromophore in a Molecular Cavity via the Average Solvent Electrostatic Configuration Model

T2 - Applications in Rhodopsin and Rhodopsin-Mimicking Systems

AU - Nikolaev, Dmitrii M.

AU - Manathunga, Madushanka

AU - Orozco-Gonzalez, Yoelvis

AU - Shtyrov, Andrey A.

AU - Guerrero Martinez, Yansel Omar

AU - Gozem, Samer

AU - Ryazantsev, Mikhail N.

AU - Coutinho, Kaline

AU - Canuto, Sylvio

AU - Olivucci, Massimo

N1 - Funding Information: M.O. is grateful to the Center for Photochemical Sciences of the Bowling Green State University, the Human Frontier Science Program Organization under Grant RGP0049/385, the National Science Foundation under Grant CHE-1152070, and the Institute for Advanced Studies of the University of Strasbourg for a USIAS fellowship. The research was supported by the Ohio Super-computing Center (OSC). The results of the work were obtained using computational resources of Peter the Great Saint-Petersburg Polytechnic University Supercomputing Center ( www.spbstu.ru ). The work has been performed under the Project HPC-EUROPA3 (INFRAIA-2016-1-730897), with the support of the EC Research Innovation Action under the H2020 Programme; in particular, the D.M.N. and M.N.R. gratefully acknowledge the support of Prof. Massimo Olivucci and the computing resources and technical support provided by CINECA. M.N.R. acknowledges funding by St. Petersburg State University, travel grant COLLAB2019_2 (No. 41131617). S.G. acknowledges the NSF for its support through Grant CHE-2047667 and for computational resources through XSEDE research allocation CHE180027. K.C and S.C. thank the Brazilian funding agencies for Grants 2014/50983-3 of FAPESP and 465259/2014-6 of CNPq from the National Institute of Science and Technology Complex Fluids (INCT-FCx) and Grant 23038.004630/2014-35 of CAPES from the BioMol project. Code development for the application of FEP methodology for rPSB in the protein environment was supported by RSF under Grant 20-13-00303. Publisher Copyright: © 2021 American Chemical Society

PY - 2021/8/11

Y1 - 2021/8/11

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.

KW - TRANSITION-STATE OPTIMIZATION

KW - ANABAENA SENSORY RHODOPSIN

KW - SELF-CONSISTENT-FIELD

KW - MONTE-CARLO

KW - GEOMETRY OPTIMIZATION

KW - AQUEOUS-SOLUTION

KW - GRADIENT-METHOD

KW - HIGH-THROUGHPUT

KW - FORCE-FIELD

KW - QM/MM

UR - https://www.mendeley.com/catalogue/58c58e14-0357-32b5-a07f-cd0f18c8e1e3/

UR - http://www.scopus.com/inward/record.url?scp=85113921538&partnerID=8YFLogxK

U2 - 10.1021/acs.jctc.1c00221

DO - 10.1021/acs.jctc.1c00221

M3 - статья

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 -