Investigation of some peptide ligands by molecular dynamics simulation methods.

Understanding the dynamics and mechanism of protein folding as well secondary structure continues to be the central problems in bioscience. Computer simulations act as a bridge between microscopic length and time scales and the macroscopic world of the laboratory. Molecular dynamics simulations represent a powerfull tool to gain insight into the structure and dynamics of complex macromolecular systems. On the otherhand, with standard MD simulations at low temperatures, an explicitly solvated protein or peptide generally becomes trapped in any of many local energy minima, prohibiting a representative sampling of the entire range of conformations. Of a few suggested solutions, REMD is least time-consuming, easiest to implement, and theoretically sound. In this metod, a number of simulations are performed at different temperatures in parellel, and exchanges of configurations are tried periodically.In this thesis, the conformational states of three different peptide sequences that bind to Staphylococcal enterotoxin B (SEB) and of their repeating sequences were sampled by Molecular Dynamics (MD) and Replica-exchange molecular dynamic simulations (REMD) in explicit water. During simulations, changes in the secondary structure having peptides have been obtained. We have also obtained the free-energy landscapes (FEL) of each peptide by principal component analysis, to understand how the secondary structural properties change according to temperature. From the analysis of REMD results, we also calculated hydrophobic and hydrophilic solvent accessible surface areas (SASA) and the number of hydrogen bonds for all peptides.The information obtained MD and REMD simulations exhibit that the peptide sequences have mostly random coil, bend and turn structures and these structures change with temperature and the initial conditions of simulations. Addionally, it has been observed that the hydrophobic segments of the peptides tend to form bend or turn structures. The results obtained were compared with the experimental results in the literature and it has been seen these results are consistent with each other.