6533b828fe1ef96bd1288cec

RESEARCH PRODUCT

Exploring Chemical Reactivity in Enzyme Catalyzed Processes Using QM/MM Methods: An Application to Dihydrofolate Reductase

J. Javier Ruiz-perníaIñaki TuñónVicent Moliner

subject

Chemical processQuantitative Biology::BiomoleculesbiologyChemistryProtein dynamicsMolecular mechanicsEnzyme catalysisQM/MMTransition state theoryMolecular dynamicsBiochemistryChemical physicsDihydrofolate reductasebiology.protein

description

Enzymes are the catalysts used by living organisms to accelerate chemical processes under physiological conditions. In this chapter, we illustrate the current view about the origin of their extraordinary rate enhancement based on molecular simulations and, in particular, on methods based on the combination of Quantum Mechanics and Molecular Mechanics potentials which provide a solution to treat the chemical reactivity of these large and complex molecular systems. Computational studies on Dihydrofolate Reductase have been selected as a conductor wire to present the evolution and difficulties to model chemical reactivity in enzymes. The results discussed here show that experimental observations can be currently understood within the framework of Transition State Theory provided that the adequate simulations are carried out. Protein dynamics, quantum tunnelling effects and conformational diversity are essential ingredients to explain the complex behaviour of these amazing molecular machineries.

yearjournalcountryeditionlanguage
2015-01-01
https://doi.org/10.1007/978-3-319-21626-3_15