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In this tutorial review we show how the methods and techniques of computational chemistry have been applied to the understanding of the physical basis of the rate enhancement of chemical reactions by enzymes. This is to answer the question: Why is the activation free energy in enzyme catalysed reactions smaller than the activation free energy observed in(More)
The ability to design effective enzymes is one of the most fundamental challenges in biotechnology and in some respects in biochemistry. In fact, such ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. In this work, we explore the reliability of different simulation approaches, in terms of(More)
Elucidating the relationship between the folding landscape of enzymes and their catalytic power has been one of the challenges of modern enzymology. The present work explores this issue by using a simplified folding model to generate the free-energy landscape of an enzyme and then to evaluate the activation barriers for the chemical step in different(More)
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(More)
The possible relationship between the thermal stability and the catalytic power of enzymes is of great current interest. In particular, it has been suggested that thermophilic or hyperthermophilic (Tm) enzymes have lower catalytic power at a given temperature than the corresponding mesophilic (Ms) enzymes, because the thermophilic enzymes are less flexible(More)
The ability to predict the thermal stability of proteins based on their corresponding sequence is a problem of great fundamental and practical importance. Here we report an approach for calculating the electrostatic contribution to protein stability based on the use of the semimacroscopic protein dipole Langevin dipole (PDLD/S) in its linear response(More)
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(More)
Evaluating the free-energy landscape of proteins and the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of simplified coarse-grained (CG) folding models offers an effective way of(More)
The ability to predict the absolute stability of proteins based on their corresponding sequence and structure is a problem of great fundamental and practical importance. In this work, we report an extensive, refinement and validation of our recent approach (Roca et al., FEBS Lett 2007;581:2065-2071) for predicting absolute values of protein stability(More)
The way in which enzymes influence the rate of chemical processes is still a question of debate. The protein promotes the catalysis of biochemical processes by lowering the free energy barrier in comparison with the reference uncatalyzed reaction in solution. In this article we are reporting static and dynamic aspects of the enzyme catalysis in a(More)