title: Molecular Mechanism of Wide Photoabsorption Spectral Shifts of Color Variants of Human Cellular Retinol Binding Protein II.
abstract: Color variants of human cellular retinol binding protein II (hCRBPII) created by protein engineering were recently shown to exhibit anomalously wide photoabsorption spectral shifts over ∼200 nm across the visible region. The remarkable phenomenon provides a unique opportunity to gain insight into the molecular basis of the color tuning of retinal binding proteins for understanding of color vision as well as for engineering of novel color variants of retinal binding photoreceptor proteins employed in optogenetics. Here, we report a theoretical investigation of the molecular mechanism underlying the anomalously wide spectral shifts of the color variants of hCRBPII. Computational modeling of the color variants with hybrid molecular simulations of free energy geometry optimization succeeded in reproducing the experimentally observed wide spectral shifts, and revealed that protein flexibility, through which the active site structure of the protein and bound water molecules is altered by remote mutations, plays a significant role in inducing the large spectral shifts.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Kamiya
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D003116:Color; D018360:Crystallography, X-Ray; D006801:Humans; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D054840:Retinol-Binding Proteins, Cellular / Q000737:chemistry*
chemical_list: D054840:Retinol-Binding Proteins, Cellular