Listar por autoría "cb70cd97-d8f5-4d84-a497-01b952becc2d"
Mostrando ítems 1-20 de 29
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A computational study of the phosphoryl transfer reaction between ATP and Dha in Aqueous Solution
Bordes, Isabel; Ruiz-Pernía, José Javier; Castillo, Raquel; Moliner, Vicent Royal Society of Chemistry (2015)Phosphoryl transfer reactions are ubiquitous in biology, being involved in processes ranging from energy and signal transduction to the replication genetic material. Dihydroxyacetone phosphate (Dha-P), an intermediate ... -
A Novel Strategy to Study Electrostatic Effects in Chemical Reactions: Differences between the Role of Solvent and the Active Site of Chalcone Isomerase in a Michael Addition
Ruiz-Pernía, José Javier; Martí Forés, Sergio; Moliner, Vicent; Tuñón, Iñaki American Chemical Society (2012)The electrostatic behavior of active site residues in enzyme catalysis is quite different from that of water molecules in solution. To highlight the electrostatic differences between both environments, we propose a QM/MM ... -
A QM/MM study of the reaction mechanism for the 3′-processing step catalyzed by HIV-1 integrase
Ruiz-Pernía, José Javier; Nahum Alves, Cláudio; Moliner, Vicent; Silla, Estanislao; Tuñón, Iñaki Elsevier (2009)Integrase (IN) is one of the three human immunodeficiency virus type 1 enzymes (HIV-1) essential for effective viral replication. This viral enzyme is involved in the integration of HIV DNA into host chromosomal DNA. In ... -
Chemical Ligation and Isotope Labeling to Locate Dynamic Effects during Catalysis by Dihydrofolate Reductase
Luk, Louis Y. P.; Ruiz-Pernía, José Javier; Adesina, Aduragbemi S.; Loveridge, E. Joel; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K. Wiley (2015-07-27)Experimental and computational approaches have long been employed to define the role of protein motions in en- zyme catalysis, but a refined experimental method for locating the origin of dynamic effects has not previously ... -
Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformatión for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases
Soliman, Mahmoud E. S.; Ruggiero, Giuseppe D.; Ruiz-Pernía, José Javier; Greig, Ian R.; Williams, Ian H. Royal Society of Chemistry (2009)Molecular dynamics simulations have been performed for non-covalent complexes of phenyl b-xylobioside with the retaining endo-b-1,4-xylanase from B. circulans (BCX) and its Tyr69Phe mutant using a hybrid QM/MM methodology. ... -
Does glycosyl transfer involve an oxacarbenium intermediate? Computational simulation of the lifetime of the methoxymethyl cation in water
Williams, Ian H.; Ruiz-Pernía, José Javier; Tuñón, Iñaki International Union of Pure and Applied Chemistry (2011)2D free-energy surfaces for transfer of the methoxymethyl cation between two water molecules are constructed from molecular dynamics (MD) simulations in which these atoms are treated quantum-mechanically within a box of ... -
Dynamic effects on reaction rates in a Michael Addition catalyzed by Chalcone Isomerase. Beyond the frozen environment approach
Ruiz-Pernía, José Javier; Tuñón, Iñaki; Moliner, Vicent; Hynes, James T.; Roca, Maite American Chemical Society (2008)We present a detailed microscopic study of the dynamics of the Michael addition reaction leading from 6′-deoxychalcone to the corresponding flavanone. The reaction dynamics are analyzed for both the uncatalyzed reaction ... -
Elucidation of the Active Form and Reaction Mechanism in Human Asparaginase Type III Using Multiscale Simulations
Anđelković, Milorad; Zinovjev, Kirill; Ramos Guzmán, Carlos Alberto; Ruiz-Pernía, José Javier; Tuñón, Iñaki American Chemical Society (2023-08-27)l-asparaginases catalyze the asparagine hydrolysis to aspartate. These enzymes play an important role in the treatment of acute lymphoblastic leukemia because these cells are unable to produce their own asparagine. Due to ... -
Ensemble-Averaged QM/MM Kinetic Isotope Effects for the SN2 Reaction of Cyanide Anions with Chloroethane in DMSO Solution
Ruiz-Pernía, José Javier; Williams, Ian H. Wiley (2012-07)The existence of solvent fluctuations leads to populations of reactant-state (RS) and transition-state (TS) configurations and implies that property calculations must include appropriate averaging over distributions of ... -
Hydrolysis of Phosphotriesters: A Theoretical Analysis of the Enzymatic and Solution Mechanisms
López Canut, Violeta; Ruiz-Pernía, José Javier; Castillo, Raquel; Moliner, Vicent; Tuñón, Iñaki Wiley (2012-07)A theoretical study on the alkaline hydrolysis of paraoxon, one of the most popular organophosphorus pesticides, in aqueous solution and in the active site of Pseudomonas diminuta phosphotriesterase (PTE) is presented. ... -
Increased Dynamic Effects in a Catalytically Compromised Variant of Escherichia coli Dihydrofolate Reductase
Ruiz-Pernía, José Javier; Luk, Louis Y. P.; García Meseguer, Rafael; Martí Forés, Sergio; Loveridge, E. Joel; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K. American Chemical Society (2013)Isotopic substitution (15N, 13C, 2H) of a catalytically compromised variant of Escherichia coli dihydrofolate reductase, EcDHFR-N23PP/S148A, has been used to investigate the effect of these mutations on catalysis. The ... -
Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State
Behiry, Enas; Ruiz-Pernía, José Javier; Luk, Louis Y. P.; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K. Wiley (2018-03-12)The origin of substrate preference in promiscuous enzymes was investigated by enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus stearothermophilus (BsADH). At physiological temperature, protein dynamic ... -
Linking Electrostatic Effects and Protein Motions in Enzymatic Catalysis. A Theoretical Analysis of Catechol O-Methyltransferase
García Meseguer, Rafael; Zinovjev, Kirill; Roca, Maite; Ruiz-Pernía, José Javier; Tuñón, Iñaki American Chemical Society (2015-08)The role of protein motions in enzymatic catalysis is the subject of a hot scientific debate. We here propose the use of an explicit solvent coordinate to analyze the impact of environmental motions during the reaction ... -
Loss of Hyperconjugative Effects Drives Hydride Transfer during Dihydrofolate Reductase Catalysis
Angelastro, Antonio; Ruiz-Pernía, José Javier; Tuñón, Iñaki; Moliner, Vicent; Luk, Louis Y. P.; Allemann, Rudolf K. American Chemical Society (2019-09-23)Hydride transfer is widespread in nature and has an essential role in applied research. However, the mechanisms of how this transformation occurs in living organisms remain a matter of vigorous debate. Here, we examined ... -
Mechanism of glycoside hydrolysis: a comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanases
Soliman, Mahmoud E. S.; Ruiz-Pernía, José Javier; Greig, Ian R.; Williams, Ian H. Royal Society of Chemistry (2009)Computational simulations have been performed using hybrid quantum-mechanical/ molecular-mechanical potentials to investigate the catalytic mechanism of the retaining endo-b-1, 4-xylanase (BCX) from B. circulans. ... -
Minimization of dynamic effects in the evolution of dihydrofolate reductase
Ruiz-Pernía, José Javier; Behiry, Enas; Luk, Louis Y. P.; Loveridge, E. Joel; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K. Royal Society of Chemistry (2016)Protein isotope labeling is a powerful technique to probe functionally important motions in enzyme catalysis and can be applied to investigate the conformational dynamics of proteins. Previous investigations have indicated ... -
Protein Isotope Effects in Dihydrofolate Reductase From Geobacillus stearothermophilus Show Entropic–Enthalpic Compensatory Effects on the Rate Constant
Luk, Louis Y. P.; Ruiz-Pernía, José Javier; Dawson, William M.; Loveridge, E. Joel; Tuñón, Iñaki; Moliner, Vicent; Allemann, Rudolf K. American Chemical Society (2014)Catalysis by dihydrofolate reductase from the moderately thermophilic bacterium Geobacillus stearothermophilus (BsDHFR) was investigated by isotope substitution of the enzyme. The enzyme kinetic isotope effect for hydride ... -
QM/MM kinetic isotope effects for chloromethane hydrolysis in water
Ruiz-Pernía, José Javier; Ruggiero, Giuseppe D.; Williams, Ian H. John Wiley & Sons (2013)Computational simulations for chloromethane hydrolysis have been performed using hybrid quantum-mechanical/molecular-mechanical methods with explicit solvation by large numbers of water molecules. In the first part of the ... -
QM/MM simulations for methyl transfer in solution and catalysed by COMT: ensemble-averaging of kinetic isotope effects
Kanaan Izquierdo, Natalia; Ruiz-Pernía, José Javier; Williams, Ian H. Royal Society of Chemistry (2008)Sampling of structures from QM/MM molecular dynamics reveals distinct families of reactant-state conformers and yields kinetic isotope effects for reactions in enzyme active sites and in solution, averaged over thermal ... -
QM/MM Study of L-Lactate Oxidation by Flavocytochrome b2
Ruiz-Pernía, José Javier; de la LANDE, Aurélien; Lévy, B.; Lederer, F.; Demachy, I.; Moliner, Vicent; Guillet, Natacha Royal Society of Chemistry (2016-05-18)In this work, we have performed molecular dynamics simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) scheme to study the mechanism of L-lactate oxidation by flavocytochrome b2 (Fcb2). Our results ...