An Average Solvent Electrostatic Configuration Protocol for QM/MM Free Energy Optimization: Implementation and Application to Rhodopsin Systems

Orozco‐Gonzalez, Yoelvis; Manathunga, Madushanka; Marín, María del Carmen; Agathangelou, Damianos; Jung, Kwang‐Hwan; Melaccio, Federico; Ferré, Nicolas; Haacke, S.; Coutinho, Kaline; Canuto, Sylvio; Olivucci, Massimo

doi:10.1021/acs.jctc.7b00860

Cited by 33 publications

(52 citation statements)

References 71 publications

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“…The 300 K Boltzmann distribution of Z - 1 and E - 2 in methanol has been simulated by combining 40 the Average Solvent Electrostatic Configuration (ASEC) model 41 and the free energy gradient method proposed by Nagaoka et al 42 . A representative Franck-Condon structure has then been obtained by energy minimization of the ASEC snapshot with the excitation energy closest to the average (Supplementary Notes 1 and 2 , and Supplementary Figs 3 – 5 43 .…”

Section: Methodsmentioning

confidence: 99%

Engineering the vibrational coherence of vision into a synthetic molecular device

Gueye¹,

Manathunga²,

Agathangelou³

et al. 2018

Nat Commun

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The light-induced double-bond isomerization of the visual pigment rhodopsin operates a molecular-level optomechanical energy transduction, which triggers a crucial protein structure change. In fact, rhodopsin isomerization occurs according to a unique, ultrafast mechanism that preserves mode-specific vibrational coherence all the way from the reactant excited state to the primary photoproduct ground state. The engineering of such an energy-funnelling function in synthetic compounds would pave the way towards biomimetic molecular machines capable of achieving optimum light-to-mechanical energy conversion. Here we use resonance and off-resonance vibrational coherence spectroscopy to demonstrate that a rhodopsin-like isomerization operates in a biomimetic molecular switch in solution. Furthermore, by using quantum chemical simulations, we show why the observed coherent nuclear motion critically depends on minor chemical modifications capable to induce specific geometric and electronic effects. This finding provides a strategy for engineering vibrationally coherent motions in other synthetic systems.

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Section: Methodsmentioning

confidence: 99%

Engineering the vibrational coherence of vision into a synthetic molecular device

Gueye¹,

Manathunga²,

Agathangelou³

et al. 2018

Nat Commun

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“…The QM/MM calculations of NQO-WT were performed using the Average Solvent Electrostatic Configuration -Free Energy Gradient (ASEC-FEG) protocol. The ASEC-FEG approach combines the idea of the Average Solvent Electrostatic Configuration model, 37,38 originally developed to study molecular systems in solution, and the Free Energy Gradient method proposed by Nagaoka et al [39][40][41] ASEC-FEG has been extended to proteins by including van der Waals average interaction energy 42 and has recently been extended to model flavoproteins. 43 Therefore, the word "Solvent" in our ASEC simulations really encompasses both the solvent and protein.…”

Section: Methodsmentioning

confidence: 99%

The Ionic Atmosphere Effect on the Absorption Spectrum of a Flavoprotein: A Reminder to Consider the Importance of Solution Ions

Dratch

Orozco‐Gonzalez

Gadda

et al. 2021

Preprint

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Ionizable residues and monoatomic ions in solution modulate enzyme catalysis and the structural stability of proteins; however, the delicate interplay between these short-range charges and longrange charges, and their contributions to the electrostatic environment in a protein active site, is currently not fully understood. The study presented here utilizes the FMN-dependent NADH:quinone oxidoreductase from Pseudomonas aeruginosa PAO1 (NQO, EC 1.6.5.9, UniProtKB Q9I4V0) as a model system to study the effect of introducing an active site negative charge on the flavin absorption spectrum both in the absence and presence of a long-range electrostatic potential coming from solution ions. Using pH-dependent UV-visible spectroscopy, there were no observed changes in the flavin absorption spectrum when an active site tyrosine (Y277) deprotonated in vitro. These results could only be reproduced computationally using Average Solvent Electrostatic Configuration (ASEC) hybrid quantum mechanics / molecular mechanics (QM/MM) simulations that included both positive and negative solution ions. The same calculations performed with minimal ions to neutralize protein charges predicted that deprotonating Y277 would significantly affect the flavin absorption spectrum. Analyzing the distribution of solution ions from ASEC and radial distribution functions derived from molecular dynamics indicated that the solution ions reorganize around the protein surface upon Y277 deprotonation to cancel the effect of the tyrosinate on the flavin absorption spectrum. Biochemical experiments were performed to support this hypothesis. This work highlights the importance of salt ions, which are sometimes overlooked, since they can contribute a non-uniform and anisotropic long-range potential to the electrostatic environment of an active site.

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“…L83Q, the blue-most shifted mutant, surprisingly shows the opposite effect, with the 13C isomer being 6 nm red-shifted with respect to AT. From a purely computational structure of the mutated protein-chromophore complexes, obtained by the automatic retinal protein model (ARM) [106], the mutation-induced shifts were correctly reproduced, as well as the amount of LA-induced blue-shifts for W76F and V112N. For L83Q, ARM produced a wrong orientation of the dipoles of Q83, which was corrected "manually".…”

Section: A Effect Of Mutations On the Esl: Rationalising Spectral Shmentioning

confidence: 98%

Sub-picosecond C=C bond photo-isomerization: evidence for the role of excited state mixing

Agathangelou¹,

Roy²,

Marín³

et al. 2021

Comptes Rendus. Physique

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Sub-picosecond photo-isomerization is the major primary process of energy conversion in retinal proteins and has as such been in the focus of extensive theoretical and experimental work over the past decades. In this review article, we revisit the long-standing question as to how the protein tunes the isomerization speed and quantum yield. We focus on our recent contributions to this field, which underscore the concept of a delicate mixing of reactive and non-reactive excited states, as a result of steric properties and electrostatic interactions with the protein environment. Further avenues and new approaches are outlined which hold promise for advancing our understanding of these intimately coupled chromophore-protein systems. Résumé

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An Average Solvent Electrostatic Configuration Protocol for QM/MM Free Energy Optimization: Implementation and Application to Rhodopsin Systems

Cited by 33 publications

References 71 publications

Engineering the vibrational coherence of vision into a synthetic molecular device

Engineering the vibrational coherence of vision into a synthetic molecular device

The Ionic Atmosphere Effect on the Absorption Spectrum of a Flavoprotein: A Reminder to Consider the Importance of Solution Ions

Sub-picosecond C=C bond photo-isomerization: evidence for the role of excited state mixing

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