SUPERVISOR: Drazen PETROV

PROJECT ASSIGNED TO: Nadine GRUNDSCHOBER

Amino acids are not only crucial to ensure the function and stability of a protein, but also influence the binding of molecules to the protein. The mutation of an amino acid in a protein may affect the direct binding affinity, or the conformational ensemble of the protein itself. To understand the behavior and the interaction with a buffer or a ligand, it is essential to investigate the core units of a protein, the amino acids.

This research aims to characterize amino acids in different environments, for example in a protein or buffer, using accelerated enveloping distribution sampling (A-EDS). The advantage of A-EDS is that multiple free-energy differences can be calculated from a single molecular dynamics simulation. Doing so, a reference Hamiltonian, which samples the conformational space of all desired end-states, is constructed. To describe the influence of amino acid mutations on the dynamics in the active site of a protein, suitable parameters for A-EDS need to be determined.
For this several combinations of amino acids and parameters for A-EDS calculations will be investigated. Using the obtained parameter set several amino acid mutations that may affect the direct binding affinity can be tested at the same time using A-EDS. This might lead to the identification of hot spots in the active site of the target protein.