SNSF | P3 Research Database

ENZYMATIC REACTIONS; QUANTUM/CLASSICAL DYNA-; PROTON TRANSFER REACTIONS; ELECTRONCOUPLED PROTON; REACTIVE DYNAMICS; MIXED; MICS; SOLVATION EFFECTS; Computer Simulations; Computational Biophysics; Catalysis; Intermolecular Interactions

English title	Intermolecular Interactions and the Role of Dynamics in Enzymatic Catalysis
Applicant	Meuwly Markus
Number	114814
Funding scheme	SNSF Professorships
Research institution	Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education	University of Basel - BS
Main discipline	Physical Chemistry
Start/End	01.10.2006 - 30.09.2007
Approved amount	210'673.00

Lead

Lay summary
Over the past decade, "Computational Science" has emerged as a new discipline. In a broad sense, this subject includes all research areas of Science where computer simulation plays the leading role in the quest for new knowledge and understanding. The field bridges the gap between the two classical approaches to scientific research: theory and experiment. Paramount to the unprecedented rise of the importance of computer-based work is a dramatic increase in the power of computers. The main impetus for pursuing computational sciences is the desire to solve problems which are not accessible otherwise.The investigation of intermolecular interactions and the role of dynamics in enzymatic catalysis is paradigmatic for a computational approach to scientific questions. Experimental work alone can not unravel the physical, chemical and biological driving forces for enzymatic reactions. On the other hand, theoretical methods have their limitations due to the large number of degrees of freedom involved. This is why a carefully developed computational model, gauged with respect to experimental data, can give invaluable information about atomistic details involved in catalysis. Chemical reactions, in particular enzymatic reactions, are among the most important processes relevant to living organisms. Their understanding depends critically on an accurate description of the intermolecular interactions between the participating molecules and the nuclear dynamics of the atoms involved.For this project we develop numerical methods and computational strategies to understand the energetics and dynamics of chemical reactions in complex systems. Because many degrees of freedom are involved (often several 10000), a simplified energy expression based on a model that represents chemical bonds by harmonic, i.e. ideal, springs is used. However, for more detailed investigations, such as the infrared spectroscopy of small molecules (a very powerful method) in a protein environment, or the binding of pharmacologically relevant molecules still much work in improving the predictive power of force fields remains. With a combination of improved force fields and quantum chemical calculations we investigate chemical reactions including hydrogen/proton-transfer, ligand-binding and electron-coupled proton transfer at a quantitative level.Systems of particular interest for this research include myoglobin (responsible for storage and transport of oxygen), HIV-I protease (a major player in HIV) and CDK2, a common drug target in pharmaceutical research. Most of the work is carried out in collaboration with experimental groups in Switzerland and abroad.

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Last update: 21.02.2013