Our aim was to characterize the structural-dynamical changes during ligand binding of the homodimeric Ca2+-binding S100A4 protein. To this end, we generated structural ensembles that reflect the experimentally determined internal dynamics of the free molecule as well as its form bound to nonmuscle myosin IIA (NMIIA). These data were determined earlier by the student, Gyula Pálfy. These parameters were included as restraints in ensemble molecular dynamics simulations using a version of the GROMACS package modified by the mentor, Zoltán Gáspári. Detailed comparative analysis of the generated ensembles is expected to allow the identification of the structural-dynamical changes upon ligand binding and inferring their functional relevance.

Gyula learned the usage of GROMACS and the principles of multi-replica molecular dynamics simulations. We computed a 20 ns long unrestrained simulation for free S100A4 and have performed a number of exploratory runs to obtain the best parametrization for the restrained simulations. We found that the initial PDB structure used for simulation should be applied with as minimal changes as possible. Further simulations and their analysis are continued beyond the duration of the grant period.

During the program Gyula established a good and effective cooperation not only with the Mentor but also with his PhD student Bertalan Kovács, therefore the program was successful in terms of improvement of professional skills as well as in strengthening the long-term cooperation of the two research groups.

Zoltán Gáspári - Gyula Pálfy