scholarly journals The protonation state of Glu202 in acetylcholinesterase

2021 ◽  
Author(s):  
Jiye Wang ◽  
Suitian Lai ◽  
Yichao Kong ◽  
Weixuan Yao ◽  
Xiabin Chen ◽  
...  
Keyword(s):  
Protonation State

Distinguishing two groups of flavin reductases by analyzing the protonation state of an active site carboxylic acid

2011 ◽  
Vol 79 (7) ◽  
pp. 2076-2085 ◽  
Author(s):  
Verónica I. Dumit ◽  
Néstor Cortez ◽  
G. Matthias Ullmann
Keyword(s):  
Carboxylic Acid ◽  
Active Site ◽  
Protonation State

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

scholarly journals Inhibitor Binding Influences the Protonation State of Histidines in SARS-CoV-2 Main Protease

2021 ◽  
Vol 120 (3) ◽  
pp. 204a-205a
Author(s):  
Anna Pavlova ◽  
Diane L. Lynch ◽  
Micholas Dean Smith ◽  
Jeremy D. Smith ◽  
James C. Gumbart
Keyword(s):  
Protonation State ◽  
Inhibitor Binding ◽  
Main Protease

scholarly journals A QM/MM Evaluation of the Missing Step in the Reduction Mechanism of HMG-CoA by Human HMG-CoA Reductase

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1085
Author(s):  
Paula Mihaljević-Jurič ◽  
Sérgio F. Sousa
Keyword(s):  
Mevalonate Pathway ◽  
Atomic Level ◽  
Amino Acid Residues ◽  
Protonation State ◽  
Primary Target ◽  
Cholesterol Levels ◽  
The Subject ◽  
Electron Reduction ◽  
Dynamics Simulations ◽  
Coa Reductase

Statins are important drugs in the regulation of cholesterol levels in the human body that have as a primary target the enzyme β-hydroxy-β-methylglutaryl-CoA reductase (HMGR). This enzyme plays a crucial role in the mevalonate pathway, catalyzing the four-electron reduction of HMG-CoA to mevalonate. A second reduction step of this reaction mechanism has been the subject of much speculation in the literature, with different conflicting theories persisting to the present day. In this study, the different mechanistic hypotheses were evaluated with atomic-level detail through a combination of molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The obtained Gibbs free activation and Gibbs free reaction energy (15 kcal mol−1 and −40 kcal mol−1) show that this hydride step takes place with the involvement of a cationic His405 and Lys639, and a neutral Glu98, while Asp715 remains in an anionic state. The results provide an atomic-level portrait of this step, clearly demonstrating the nature and protonation state of the amino acid residues involved, the energetics associated, and the structure and charge of the key participating atoms in the several intermediate states, finally elucidating this missing step.

scholarly journals How Active-Site Protonation State Influences the Reactivity and Ligation of the Heme in Chlorite Dismutase

2010 ◽  
Vol 132 (16) ◽  
pp. 5711-5724 ◽  
Author(s):  
Bennett R. Streit ◽  
Béatrice Blanc ◽  
Gudrun S. Lukat-Rodgers ◽  
Kenton R. Rodgers ◽  
Jennifer L. DuBois
Keyword(s):  
Active Site ◽  
Protonation State ◽  
Chlorite Dismutase

Effects of Protonation State on a Tyrosine−Histidine Bioinspired Redox Mediator†

2010 ◽  
Vol 114 (45) ◽  
pp. 14450-14457 ◽  
Author(s):  
Gary F. Moore ◽  
Michael Hambourger ◽  
Gerdenis Kodis ◽  
Weston Michl ◽  
Devens Gust ◽  
...  
Keyword(s):  
Redox Mediator ◽  
Protonation State

scholarly journals Cavity hydration dynamics in cytochrome c oxidase and functional implications

2017 ◽  
Vol 114 (42) ◽  
pp. E8830-E8836 ◽  
Author(s):  
Chang Yun Son ◽  
Arun Yethiraj ◽  
Qiang Cui
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Proton Transfer ◽  
Molecular Dynamics Simulations ◽  
Transmembrane Protein ◽  
Wetting Transition ◽  
Protonation State ◽  
Hydration Level ◽  
Level Change ◽  
Dynamics Simulations

Cytochrome c oxidase (CcO) is a transmembrane protein that uses the free energy of O2 reduction to generate the proton concentration gradient across the membrane. The regulation of competitive proton transfer pathways has been established to be essential to the vectorial transport efficiency of CcO, yet the underlying mechanism at the molecular level remains lacking. Recent studies have highlighted the potential importance of hydration-level change in an internal cavity that connects the proton entrance channel, the site of O2 reduction, and the putative proton exit route. In this work, we use atomistic molecular dynamics simulations to investigate the energetics and timescales associated with the volume fluctuation and hydration-level change in this central cavity. Extensive unrestrained molecular dynamics simulations (accumulatively ∼4 μs) and free energy computations for different chemical states of CcO support a model in which the volume and hydration level of the cavity are regulated by the protonation state of a propionate group of heme a3 and, to a lesser degree, the redox state of heme a and protonation state of Glu286. Markov-state model analysis of ∼2-μs trajectories suggests that hydration-level change occurs on the timescale of 100–200 ns before the proton-loading site is protonated. The computed energetic and kinetic features for the cavity wetting transition suggest that reversible hydration-level change of the cavity can indeed be a key factor that regulates the branching of proton transfer events and therefore contributes to the vectorial efficiency of proton transport.

The pKa value of the proximal water molecule trans to a high-valent MnVO porphyrin: towards the control of reactivity by pH

2017 ◽  
Vol 46 (36) ◽  
pp. 12088-12094 ◽  
Author(s):  
Laurie Saint-Germes ◽  
Laure Bar ◽  
Jérôme Dejeu ◽  
Nicolas Spinelli ◽  
Eric Defrancq ◽  
...  
Keyword(s):  
Water Molecule ◽  
Hydroxyl Group ◽  
Protonation State ◽  
Pka Value ◽  
High Valent

In water, the protonation state of the proximal water molecule of a high-valent manganese-oxo porphyrin could be controlled by pH. While in interaction with DNA the porphyrin was able to cleave DNA, only when the proximal water molecule was in the form of a hydroxyl group.

Sign in / Sign up

Export Citation Format

Share Document