[CoII(BPyPy2COH)(OH2)2]2+: A Catalytic Pourbaix Diagram and AIMD Simulations on Four Key Intermediates

Proton reduction by [CoII(BPyPy2COH)(OH2)2]2+ (BPyPy2COH = [2,2'-bipyridin]-6-yl-di[pyridin-2-yl]methanol) proceeds through two distinct, pH-dependent pathways involving proton-coupled electron transfer (PCET), reduction and protonation steps. In this account we give an overview of the key mechanistic aspects in aqueous solution from pH 3 to 10, based on electrochemical data, time-resolved spectroscopy and ab initio molecular dynamics simulations of the key catalytic intermediates. In the acidic pH branch, a PCET to give a CoIII hydride is followed by a reduction and a protonation step, to close the catalytic cycle. At elevated pH, a reduction to CoI is observed, followed by a PCET to a CoII hydride, and the catalytic cycle is closed by a slow protonation step. In our simulation, both CoI and CoII–H feature a strong interaction with the surrounding solvent via hydrogen bonding, which is expected to foster the following catalytic step.

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Conformational Heterogeneity of a Leucine Enkephalin Analogue in Aqueous Solution and Sodium Dodecyl Sulfate Micelles: Comparison of Time-Resolved FRET and Molecular Dynamics Simulations

The Journal of Physical Chemistry B ◽

10.1021/jp903302k ◽

2009 ◽

Vol 113 (43) ◽

pp. 14381-14392 ◽

Cited By ~ 11

Author(s):

Jay R. Unruh ◽

Krzysztof Kuczera ◽

Carey K. Johnson

Keyword(s):

Molecular Dynamics ◽

Aqueous Solution ◽

Sodium Dodecyl Sulfate ◽

Molecular Dynamics Simulations ◽

Sodium Dodecyl ◽

Conformational Heterogeneity ◽

Time Resolved ◽

Leucine Enkephalin ◽

Dodecyl Sulfate ◽

Dynamics Simulations

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Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 Cl−/H+ Antiporter

Molecules ◽

10.3390/molecules26226956 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6956

Author(s):

Ekaterina Kots ◽

Derek M. Shore ◽

Harel Weinstein

Keyword(s):

Force Field ◽

Conformational Changes ◽

Intracellular Transport ◽

Ph Dependence ◽

Linear Interpolation ◽

Acidic Ph ◽

Gating Mechanism ◽

Transporter Family ◽

Ph Dependent ◽

Dynamics Simulations

Intracellular transport of chloride by members of the CLC transporter family involves a coupled exchange between a Cl− anion and a proton (H+), which makes the transport function dependent on ambient pH. Transport activity peaks at pH 4.5 and stalls at neutral pH. However, a structure of the WT protein at acidic pH is not available, making it difficult to assess the global conformational rearrangements that support a pH-dependent gating mechanism. To enable modeling of the CLC-ec1 dimer at acidic pH, we have applied molecular dynamics simulations (MD) featuring a new force field modification scheme—termed an Equilibrium constant pH approach (ECpH). The ECpH method utilizes linear interpolation between the force field parameters of protonated and deprotonated states of titratable residues to achieve a representation of pH-dependence in a narrow range of physiological pH values. Simulations of the CLC-ec1 dimer at neutral and acidic pH comparing ECpH-MD to canonical MD, in which the pH-dependent protonation is represented by a binary scheme, substantiates the better agreement of the conformational changes and the final model with experimental data from NMR, cross-link and AFM studies, and reveals structural elements that support the gate-opening at pH 4.5, including the key glutamates Gluin and Gluex.

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Structural dynamics of P-type ATPase ion pumps

Biochemical Society Transactions ◽

10.1042/bst20190124 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1247-1257 ◽

Cited By ~ 17

Author(s):

Mateusz Dyla ◽

Sara Basse Hansen ◽

Poul Nissen ◽

Magnus Kjaergaard

Keyword(s):

Structural Dynamics ◽

Single Molecule ◽

New Technologies ◽

Atp Hydrolysis ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Time Resolved ◽

Dynamics Simulations ◽

Types Of Information ◽

P Type

Abstract P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.

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Atom Condensed Fukui Function for Condensed Phases and Biological Systems and Its Application to Enzymatic Fixation of Carbon Dioxide

10.26434/chemrxiv.9198770.v2 ◽

2019 ◽

Author(s):

Javier Oller ◽

David A. Sáez ◽

Esteban Vöhringer-Martinez

Keyword(s):

Carbon Dioxide ◽

Aqueous Solution ◽

Molecular System ◽

Chemical Reactivity ◽

Nucleophilic Attack ◽

Stable Conformation ◽

Fukui Functions ◽

Reactivity Descriptors ◽

Dynamics Simulations ◽

Fixation Of Carbon Dioxide

<div><div><div><p>Local reactivity descriptors such as atom condensed Fukui functions are promising computational tools to study chemical reactivity at specific sites within a molecule. Their applications have been mainly focused on isolated molecules in their most stable conformation without considering the effects of the surroundings. Here, we propose to combine QM/MM Born-Oppenheimer molecular dynamics simulations to obtain the microstates (configurations) of a molecular system using different representations of the molecular environment and calculate Boltzmann weighted atom condensed local reac- tivity descriptors based on conceptual DFT. Our approach takes the conformational fluctuations of the molecular system and the polarization of its electron density by the environment into account allowing us to analyze the effect of changes in the molecular environment on reactivity. In this contribution, we apply the method mentioned above to the catalytic fixation of carbon dioxide by crotonyl-CoA carboxylase/reductase and study if the enzyme alters the reactivity of its substrate compared to an aqueous solution. Our main result is that the protein en- vironment activates the substrate by the elimination of solute-solvent hydrogen bonds from aqueous solution in the two elementary steps of the reaction mechanism: the nucleophilic attack of a hydride anion from NADPH on the α, β unsaturated thioester and the electrophilic attack of carbon dioxide on the formed enolate species.</p></div></div></div>

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The X-Ray Crystallographic Structure of the Human Neonatal Fc Receptor at Acidic pH Gives Insights into pH-Dependent Conformational Changes

Protein and Peptide Letters ◽

10.2174/0929866523666160404125850 ◽

2016 ◽

Vol 23 (6) ◽

pp. 525-529 ◽

Cited By ~ 2

Author(s):

Mohammed Taha ◽

Sally E. Ward ◽

Hyun-Joo Nam

Keyword(s):

Conformational Changes ◽

Fc Receptor ◽

Crystallographic Structure ◽

Acidic Ph ◽

Neonatal Fc Receptor ◽

X Ray ◽

Ph Dependent

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A diffusion anisotropy descriptor links morphology effects of H-ZSM-5 zeolites to their catalytic cracking performance

Communications Chemistry ◽

10.1038/s42004-021-00543-w ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Xiaoliang Liu ◽

Jing Shi ◽

Guang Yang ◽

Jian Zhou ◽

Chuanming Wang ◽

...

Keyword(s):

Catalytic Activity ◽

Catalytic Cracking ◽

Catalytic Performance ◽

Zeolite Catalysts ◽

Time Resolved ◽

Cracking Performance ◽

Morphology Effect ◽

Ft Ir ◽

The Difference ◽

Dynamics Simulations

AbstractZeolite morphology is crucial in determining their catalytic activity, selectivity and stability, but quantitative descriptors of such a morphology effect are challenging to define. Here we introduce a descriptor that accounts for the morphology effect in the catalytic performances of H-ZSM-5 zeolite for C4 olefin catalytic cracking. A series of H-ZSM-5 zeolites with similar sheet-like morphology but different c-axis lengths were synthesized. We found that the catalytic activity and stability is improved in samples with longer c-axis. Combining time-resolved in-situ FT-IR spectroscopy with molecular dynamics simulations, we show that the difference in catalytic performance can be attributed to the anisotropy of the intracrystalline diffusive propensity of the olefins in different channels. Our descriptor offers mechanistic insight for the design of highly effective zeolite catalysts for olefin cracking.

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Elucidating the Onset of Plasticity in Sliding Contacts Using Differential Computational Orientation Tomography

Tribology Letters ◽

10.1007/s11249-021-01451-9 ◽

2021 ◽

Vol 69 (3) ◽

Author(s):

S. J. Eder ◽

P. G. Grützmacher ◽

M. Rodríguez Ripoll ◽

J. F. Belak

Keyword(s):

Grain Boundary ◽

Large Scale ◽

Surface Deformation ◽

Boundary Migration ◽

Material Design ◽

Lattice Rotation ◽

Time Resolved ◽

Near Surface ◽

Color Saturation ◽

Dynamics Simulations

Abstract Depending on the mechanical and thermal energy introduced to a dry sliding interface, the near-surface regions of the mated bodies may undergo plastic deformation. In this work, we use large-scale molecular dynamics simulations to generate “differential computational orientation tomographs” (dCOT) and thus highlight changes to the microstructure near tribological FCC alloy surfaces, allowing us to detect subtle differences in lattice orientation and small distances in grain boundary migration. The analysis approach compares computationally generated orientation tomographs with their undeformed counterparts via a simple image analysis filter. We use our visualization method to discuss the acting microstructural mechanisms in a load- and time-resolved fashion, focusing on sliding conditions that lead to twinning, partial lattice rotation, and grain boundary-dominated processes. Extracting and laterally averaging the color saturation value of the generated tomographs allows us to produce quantitative time- and depth-resolved maps that give a good overview of the progress and severity of near-surface deformation. Corresponding maps of the lateral standard deviation in the color saturation show evidence of homogenization processes occurring in the tribologically loaded microstructure, frequently leading to the formation of a well-defined separation between deformed and undeformed regions. When integrated into a computational materials engineering framework, our approach could help optimize material design for tribological and other deformation problems. Graphic Abstract .

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Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

The Journal of Cell Biology ◽

10.1083/jcb.200804161 ◽

2008 ◽

Vol 183 (5) ◽

pp. 865-879 ◽

Cited By ~ 122

Author(s):

Christian Frantz ◽

Gabriela Barreiro ◽

Laura Dominguez ◽

Xiaoming Chen ◽

Robert Eddy ◽

...

Keyword(s):

Actin Filament ◽

Structural Changes ◽

Ph Sensor ◽

Ph Sensitive ◽

Actin Binding ◽

Filamentous Actin ◽

Filament Dynamics ◽

Ph Dependent ◽

Dynamics Simulations

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H+ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics.

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