Photodynamics in Complex Environments: <i>Ab Initio</i> Multiple Spawning Quantum Mechanical/Molecular Mechanical Dynamics

Virshup, Aaron M.; Punwong, Chutintorn; Pogorelov, Taras V.; Lindquist, Beth A.; Ko, Chaehyuk; Martı́nez, Todd J.

doi:10.1021/jp8073464

Cited by 262 publications

(272 citation statements)

References 115 publications

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“…These energy barriers experienced by the chromophore during isomerization are caused by the protein environment as shown by model GFP chromophores, which isomerize efficiently instead of fluorescing in fluid solutions unless frozen (32)(33)(34)(35). This viewpoint is also supported by various computational studies (24,(36)(37)(38)(39). The existence of these large excited-state energy barriers leads to strong fluorescence in GFPs in contrast to other proteins, such as rhodopsin (40) and photoactive yellow protein (PYP) (41), that generically have similar PESs (Results and Discussion, A Unifying Scheme of Fluorescent and Photosensory Proteins) but are optimized for cis-trans isomerization instead of fluorescence.…”

Section: Resultsmentioning

confidence: 83%

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

Lin

Both

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Split GFPs have been widely applied for monitoring protein-protein interactions by expressing GFPs as two or more constituent parts linked to separate proteins that only fluoresce on complementing with one another. Although this complementation is typically irreversible, it has been shown previously that light accelerates dissociation of a noncovalently attached β-strand from a circularly permuted split GFP, allowing the interaction to be reversible. Reversible complementation is desirable, but photodissociation has too low of an efficiency (quantum yield <1%) to be useful as an optogenetic tool. Understanding the physical origins of this low efficiency can provide strategies to improve it. We elucidated the mechanism of strand photodissociation by measuring the dependence of its rate on light intensity and point mutations. The results show that strand photodissociation is a two-step process involving light-activated cis-trans isomerization of the chromophore followed by light-independent strand dissociation. The dependence of the rate on temperature was then used to establish a potential energy surface (PES) diagram along the photodissociation reaction coordinate. The resulting energetics-function model reveals the rate-limiting process to be the transition from the electronic excited-state to the ground-state PES accompanying cis-trans isomerization. Comparisons between split GFPs and other photosensory proteins, like photoactive yellow protein and rhodopsin, provide potential strategies for improving the photodissociation quantum yield.split GFP | potential energy surface | photodissociation | cis-trans isomerization | photosensory protein O ptical techniques for investigating biological processes in vivo can achieve subcellular spatial and millisecond temporal resolution by using genetically encoded light-responsive proteins (1). Photoactivatable proteins are used as either imaging tools, such as reversibly photoswitchable fluorescent proteins (RSFPs), with fluorescence that can be modulated by light (2) or optogenetic switches that convert light input into physiological outputs, such as channelrhodopsins, which can regulate ion flow through membranes in response to light (3). Split GFPs have been widely applied for imaging as fluorescent reporters of cellular processes, because they are small (∼25 kDa), are stable in cytosol, produce chromophores autocatalytically, and are amenable to mutation and circular permutation (4). Typically, the protein is expressed as two or more constituent parts linked to separate proteins that only fluoresce on complementing with one another, offering readouts of protein-protein colocalizaton with low background and high specificity (5). However, this technique can generate misleading results, because the GFP complexes, after being formed and fluorescing, are bound irreversibly, which can be highly perturbative to the processes being studied, especially if the protein interaction being probed is ordinarily reversible (6). Although split GFP complexes essentially do not dissocia...

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Section: Resultsmentioning

confidence: 83%

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

Lin

Both

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Further developments 12 of GPU-SA-CASSCF/AIMS will include solvent and relativistic (intersystem crossing) effects to improve the comparison between theory and experiment. [70][71][72] …”

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confidence: 99%

GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D₃

Snyder

Curchod

Martı́nez

2016

J. Phys. Chem. Lett.

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Excited-state molecular dynamics is essential to the study of photochemical reactions, which occur under nonequilibrium conditions. However, the computational cost of such simulations has often dictated compromises between accuracy and efficiency. The need for an accurate description of both the molecular electronic structure and nuclear dynamics has historically stymied the simulation of medium- to large-size molecular systems. Here, we show how to alleviate this problem by combining ab initio multiple spawning (AIMS) for the nuclear dynamics and GPU-accelerated state-averaged complete active space self-consistent field (SA-CASSCF) for the electronic structure. We demonstrate the new approach by first-principles SA-CASSCF/AIMS nonadiabatic dynamics simulation of photoinduced electrocyclic ring-opening in the 51-atom provitamin D3 molecule.

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“…In these papers, it was shown that solvent effects determined the placement and energy of conical intersection seams, as well as the coordinates that accessed them. A tendency for charge-transfer conical intersections to be stabilized by solvents excited-state potential in solvated systems has been observed in excited-state dynamics simulations 51,52 .…”

Section: Introductionmentioning

confidence: 93%

Valence-bond non-equilibrium solvation model for a twisting monomethine cyanine

McConnell

McKenzie

Olsen

2015

The Journal of Chemical Physics

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We propose and analyze a two-state valence-bond model of non-equilibrium solvation effects on the excited-state twisting reaction of monomethine cyanines. Suppression of this reaction is thought responsible for environment-dependent fluorescence yield enhancement in these dyes. Fluorescence is quenched because twisting is accompanied via the formation of dark twisted intramolecular charge-transfer (TICT) states. For monomethine cyanines, where the ground state is a superposition of structures with different bond and charge localization, there are two possible twisting pathways with different charge localization in the excited state. For parameters corresponding to symmetric monomethines, the model predicts two low-energy twisting channels on the excited-state surface that lead to a manifold of twisted intramolecular charge-transfer (TICT) states. For typical monomethines, twisting on the excited state surface will occur with a small barrier or no barrier. Changes in the solvation configuration can differentially stabilize TICT states in channels corresponding to different bonds, and that the position of a conical intersection between adiabatic states moves in response to solvation to stabilize either one channel or the other. There is a conical intersection seam that grows along the bottom of the excited-state potential with increasing solvent polarity. For monomethine cyanines with modest-sized terminal groups in moderately polar solution, the bottom of the excited-state potential surface is completely spanned by a conical intersection seam.

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Photodynamics in Complex Environments: Ab Initio Multiple Spawning Quantum Mechanical/Molecular Mechanical Dynamics

Cited by 262 publications

References 115 publications

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D₃

Valence-bond non-equilibrium solvation model for a twisting monomethine cyanine

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Photodynamics in Complex Environments: Ab Initio Multiple Spawning Quantum Mechanical/Molecular Mechanical Dynamics

Cited by 262 publications

References 115 publications

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

Mechanism and bottlenecks in strand photodissociation of split green fluorescent proteins (GFPs)

GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D3

Valence-bond non-equilibrium solvation model for a twisting monomethine cyanine

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GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D₃