Search results for "quantum theory"
showing 10 items of 234 documents
Biomimetic oxygen reduction by cofacial porphyrins at a liquid-liquid interface.
2012
Oxygen reduction catalyzed by cofacial metalloporphyrins at the 1,2-dichlorobenzene−water interface was studied with two lipophilic electron donors of similar driving force, 1,1'-dimethylferrocene (DMFc) and tetrathiafulvalene (TTF). The reaction produces mainly water and some hydrogen peroxide, but the mediator has a significant effect on the selectivity, as DMFc and the porphyrins themselves catalyze the decomposition and the further reduction of hydrogen peroxide. Density functional theory calculations indicate that the biscobaltporphyr- in, 4,5-bis(5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl))-9,9-dimethylxanthene, Co2(DPX), actually catalyzes oxygen reduction to hydrogen p…
QM/MM calculations of kinetic isotope effects in the chorismate mutase active site.
2003
Kinetic isotope effects have been computed for the Claisen rearrangement of chorismate to prephenate in aqueous solution and in the active site of chorismate mutase from B. subtilus. These included primary 13C and 18O and secondary 3H effects for substitutions at the bond-making and bond-breaking positions. The initial structures of the putative stationary points on the potential energy surface, required for the calculations of isotope effects using the CAMVIB/CAMISO programs, have been selected from hybrid QM/MM molecular dynamical simulations using the DYNAMO program. Refinement of the reactant complex and transition-state structures has been carried out by means of AM1/CHARMM24/TIP3P cal…
A Quantum Mechanic/Molecular Mechanic Study of the Wild-Type and N155S Mutant HIV-1 Integrase Complexed with Diketo Acid
2008
Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. Recently, mutation studies have been reported that have shown that a certain degree of viral resistance to diketo acids (DKAs) appears when some amino acid residues of the IN active site are mutated. Mutations represent a fascinating experimental challenge, and we invite theoretical simulations for the disclosure of still unexplored features of enzyme reactions. The aim of this work is to understand the molecular mechanisms of HIV-1 IN drug resistance, which will be useful for designing anti-HIV inhibitors with unique resistance profiles. In this study, we use mo…
Role of Protein Flexibility in Enzymatic Catalysis: Quantum Mechanical−Molecular Mechanical Study of the Deacylation Reaction in Class A β-Lactamases
2002
We present a theoretical study of a mechanism for the hydrolysis of the acyl-enzyme complex formed by a class A beta-lactamase (TEM1) and an antibiotic (penicillanate), as a part of the process of antibiotic's inactivation by this type of enzymes. In the presented mechanism the carboxylate group of a particular residue (Glu166) activates a water molecule, accepting one of its protons, and afterward transfers this proton directly to the acylated serine residue (Ser70). In our study we employed a quantum mechanics (AM1)-molecular mechanics partition scheme (QM/MM) where all the atoms of the system were allowed to relax. For this purpose we used the GRACE procedure in which part of the system …
The amorphous silica-liquid water interface studied by ab initio molecular dynamics (AIMD): local organization in global disorder
2014
International audience; The structural organization of water at a model of amorphous silica-liquid water interface is investigated by ab initio molecular dynamics (AIMD) simulations at room temperature. The amorphous surface is constructed with isolated, H-bonded vicinal and geminal silanols. In the absence of water, the silanols have orientations that depend on the local surface topology (i.e. presence of concave and convex zones). However, in the presence of liquid water, only the strong inter-silanol H-bonds are maintained, whereas the weaker ones are replaced by H-bonds formed with interfacial water molecules. All silanols are found to act as H- bond donors to water. The vicinal silanol…
Unveiling the Lewis Acid Catalyzed Diels–Alder Reactions Through the Molecular Electron Density Theory
2020
The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels&ndash
Computational study on hydrolysis of cefotaxime in gas phase and in aqueous solution
2012
We are presenting a theoretical study of the hydrolysis of a β-lactam antibiotic in gas phase and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics potentials. After exploring the potential energy surfaces at semiempirical and density functional theory (DFT) level, potentials of mean force have been computed for the reaction in solution with hybrid PM3/TIP3P calculations and corrections with the B3LYP and M06-2X functionals. Inclusion of the full molecule of the antibiotic, Cefotaxime, in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate a nucleophilic water molecule. Moreover, the flexibility of the substra…
Theoretical Study of the Catalytic Mechanism of DNA-(N4-Cytosine)-Methyltransferase from the Bacterium Proteus vulgaris
2010
In this paper the reaction mechanism for methylation of cytosine at the exocyclic N4 position catalyzed by M.PvuII has been explored by means of hybrid quantum mechanics/molecular mechanics (QM/MM) methods. A reaction model was prepared by placing a single cytosine base in the active site of the enzyme. In this model the exocyclic amino group of the base establishes hydrogen bond interactions with the hydroxyl oxygen atom of Ser53 and the carbonyl oxygen atom of Pro54. The reaction mechanism involves a direct methyl transfer from AdoMet to the N4 atom and a proton transfer from this atom to Ser53, which in turn transfers a proton to Asp96. Different timings for the proton transfers and meth…
Promiscuity in alkaline phosphatase superfamily. Unraveling evolution through molecular simulations.
2011
We here present a theoretical study of the alkaline hydrolysis of a phosphodiester (methyl p-nitrophenyl phosphate or MpNPP) in the active site of Escherichia coli alkaline phosphatase (AP), a monoesterase that also presents promiscuous activity as a diesterase. The analysis of our simulations, carried out by means of molecular dynamics (MD) simulations with hybrid quantum mechanics/molecular mechanics (QM/MM) potentials, shows that the reaction takes place through a D(N)A(N) or dissociative mechanism, the same mechanism employed by AP in the hydrolysis of monoesters. The promiscuous activity observed in this superfamily can be then explained on the basis of a conserved reaction mechanism. …
Dynamic Effects on Reaction Rates in a Michael Addition Catalyzed by Chalcone Isomerase. Beyond the Frozen Environment Approach
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 in aqueous solution and the reaction catalyzed by Chalcone Isomerase. By means of rare event simulations of trajectories started at the transition state, we have computed the transmission coefficients, obtaining 0.76 +/- 0.04 and 0.87 +/- 0.03, in water and in the enzyme, respectively. According to these simulations, the Michael addition can be seen as a formation of a new intramolecular carbon-oxygen bond accompanied by a charge transfer essentially taking place from the nu…