title: Toward an understanding of the retinal chromophore in rhodopsin mimics.
abstract: Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combined computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (λ(a)max), fluorescence (λ(f)max), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore.
authors: Department of Chemistry, Bowling Green State University, Bowling Green, Ohio 43402, USA.
authors: Mark M
authors: MM
authors: Huntress
authors: Samer
authors: S
authors: Gozem
authors: Konstantin R
authors: KR
authors: Malley
authors: Askat E
authors: AE
authors: Jailaubekov
authors: Chrysoula
authors: C
authors: Vasileiou
authors: Mikas
authors: M
authors: Vengris
authors: James H
authors: JH
authors: Geiger
authors: Babak
authors: B
authors: Borhan
authors: Igor
authors: I
authors: Schapiro
authors: Delmar S
authors: DS
authors: Larsen
authors: Massimo
authors: M
authors: Olivucci
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009154:Mutation; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012172:Retinaldehyde / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D055672:Static Electricity
chemical_list: D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D012243:Rhodopsin; D012172:Retinaldehyde