Venue: Crystal Room, Protein Center
Speaker: Dr Goutam Mukherjee
Title: Deciphering Biomolecular Recognition by Molecular Modelling Approaches
Abstract: Molecular recognition plays a pivotal role in the function of biomolecules. By considering the structure, kinetics and thermodynamics of biomolecules, it is possible to decipher the biomolecular recognition process. An understanding of this recognition process would expedite the development and generation of potent therapeutics and novel biomimetic catalysts. In this talk, I will illustrate the scope of molecular modelling for studying biomolecular recognition processes. Specifically, I will discuss alternative strategies for (i) computing proteinsmall molecule binding free energies and (ii) modelling redox protein assembly in a cellular environment. The aim of the first project is to quickly find candidate molecules that bind a target protein by enumerating a large library of small molecules or vice versa. The aim of the second project is to de novo model a full-length Cytochrome P450 (CYP), a drug-metabolizing monooxygenase enzyme, and its redox partner protein, NADPH-cytochrome P450 oxidoreductase (CPR) in a phospholipid bilayer and to study the mechanism of electron transfer between them. Application of a multiresolution simulation approach yielded multiple arrangements of CPR around CYP that are electron transfer competent. The modelled complexes allow identification of contacting residues in CYP-CPR complexes and the determinants of electron transfer rates, which agree well with available experimental data.
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