Analysis of interactions interfaces of N-terminal domain of P. aeruginosa MutL using All Atom and Coarse Grained Molecular dynamics simulation.

MIGUEL V; ARGARAÑA CE; VILLARREAL MA

Córdoba

Congreso; II Congreso Argentino de Bioinformática; 2011

We used molecular dynamics simulations (MD), using all-atom and coarse-grained models, to characterize protein-protein interaction surfaces of N-terminal domain (NTD) of Pseudomonas aeruginosa MutL. Since the crystal structure of P. aeruginosa NTD is not known, we constructed a homology model with MODELLER, using as templates the crystal structures of E. coli NTD bound to different nucleotides. After this, 200 ns MD simulations using the NTD models with or without ATP were carried out using GROMACS in order to analyze structural differences between the holo- and the apo-protein. Using cluster analysis we were able to identify the main structures in both simulations, as well as conformational differences between the apo and holo protein. With the representative structures from MD in water, we made simulations in mixed solvent (water-20% iPrOH) in order to identify areas with a high tendency to desolvate. This analysis showed two putative interaction interfaces. One could correspond to the known homologue region of E. coli dimerization and DNA binding patch, while the second interface currently has no assigned function. Simulations with coarse-grained models of free proteins showed that the second interface is capable of protein-protein interaction. This allowed us to identify the NTD dimerization interface, DNA binding patch and potential binding sites of MutL with its protein partners.