The overall goal of this research is to understand how the function of proteins of biomedical significance is affected by perturbations either deriving from the environment (such as solvent effects and binding of small molecules) or internal to the protein (such as residue mutation and oxidation). To achieve this goal, these researchers employ a combination of molecular dynamics computer simulations and quantum mechanical calculations to study how the perturbations affect the protein’s structure and dynamics. They are currently working on four projects using MSI:
- Characterizing the interplay between protein and solvent structure and dynamics for the mechanical unfolding process of spectrin repeats in dystrophin
- Identifying the mechanism by which allosteric effectors inhibit HIV-1 protease, and test whether the inhibition is additive to the one deriving from orthosteric drug binding
- Determining the molecular mechanism by which different prion protein variants have different propensity to generate unfolded neurotoxic conformations
- Characterizing the extent by which ionic strength affects the distance and orientation of helical peptides of opposite charge to be used as building blocks
Addressing these problems will help in the development of new targeted therapeutic solutions for the associated health conditions.