Building a model of the blue cone pigment based on the wild type rhodopsin structure with QM/MM methods

The Journal of Physical Chemistry. B
Jan S FrähmckeMarcus Elstner

Abstract

Understanding the mechanism of color tuning of the retinal chromophore by its host protein became one of the key issues in the research on rhodopsins. While early mutation studies addressed its genetic origin, recent studies advanced to investigate its structural origin, based on X-ray crystallographic structures. For the human cone pigments, no crystal structures have been produced, and homology models were employed to elucidate the origin of its blue-shifted absorption. In this theoretical study, we take a different route to establish a structural model for human blue. Starting from the well-resolved structure of bovine rhodopsin, we derive multiple mutant models by stepwise mutation and equilibration using molecular dynamics simulations in a hybrid quantum mechanics/molecular mechanics framework. Our 30fold mutant reproduces the experimental UV-vis absorption shift of 0.45 eV and provides new insights about both structural and genetic factors that affect the excitation energy. Electrostatic effects of individual amino acids and collaborative structural effects are analyzed using semiempirical (OM2/MRCI) and ab initio (SORCI) multireference approaches.

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Citations

Apr 9, 2015·Chemical Reviews·Alexey V Akimov, Oleg V Prezhdo
Jul 6, 2016·Journal of Chemical Theory and Computation·Deniz TunaWalter Thiel
Feb 12, 2014·Journal of the American Chemical Society·Pablo CampomanesUrsula Rothlisberger
Oct 2, 2019·The Journal of Membrane Biology·Mikhail N RyazantsevMichael F Brown
Jul 12, 2012·Physical Chemistry Chemical Physics : PCCP·Omar ValssonClaudia Filippi
Dec 25, 2013·Chemical Reviews·Oliver P ErnstHideki Kandori
May 14, 2013·Journal of Chemical Theory and Computation·Omar ValssonClaudia Filippi
Mar 22, 2018·Chemical Reviews·Uriel N MorzanDarío A Estrin
Sep 10, 2013·Journal of Chemical Theory and Computation·Mohammad WahiduzzamanThomas Heine

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