The Effect of GLY to SER Mutation on the Interaction of Hexa-Cyclio Peptides with Water: A Molecular Dynamics Simulation Study

Developments in the design of small peptides that mimic proteins in complexity, recent advances in nanosecond time-resolved spectroscopy methods to study peptides and the development of modern, highly parallel simulation algorithms have come together to give us a detailed picture of peptide folding dynamics. Recent dramatic advances in methodologies for the synthesis,modification, and analysis of peptides have increased the ease with which novel sequences can be prepared. native protein sequence, thereby allowing one to evaluate how one or more side chains contribute to the physical and biological properties of a protein. Furthermore, as our understanding of the determinants of peptide and protein structure expands, it should be increasingly possible to design peptides and proteins with predetermined structures and properties. Nevertheless, by carefully considering the structures of natural proteins and by judiciously applying computational and graphical techniques in conjunction with physical models, it appears possible to achieve this goal. Understanding the dynamics and mechanism of protein folding continues to be one of the central problems in molecular biology. Peptides have many of the features and complexities of proteins. In general, the competition between configurational entropy, hydrogen bond formation, solvation, hydrophobic coreformation and ionpair formation determines the folding rate and stability of proteins. This competition plays an essential role throughout the folding process and determines the thermodynamic equilibrium between folded and unfolded states. Modeling this competition is a standing challenge in peptide folding simulations.There are different empirical techniques for identifying the structural and dynamic aspects of the proteins. In addition to the empirical methods, molecular dynamics (MD) simulation is a powerful tool for completing and interpreting experimental results. Here, in order to study the effect of hydrophobicity of residues on the interaction of a cyclopetid with water, we simulated three hexa-cyclo peptids composed from Glycine and Serine amino acids. The considered peptides are fromed from glycine, glycine-serine and serine residues. The tree dimentioanl structures of the considered peptides were prepared by the help of protein code of Tinker suite of software package and named as CP1 for (GLY)6، CP1 for (GLY-SER)3 and CP3 for (SER)6. MD simulations were performed using NAMD package [1] and the forces between atoms were modeled with CHARMM-22 force field [2]. The results of the simulations have been analyzed in order to obtain the effect of hydrophob to hydrophil mutation on the structures and energetics of the considered systems. The structural parameters like as the number of hydrogen bonds, radiual and spatial distribution functions, orientation of water molecules and the contribution of van der Waals (vdW) and electrostatic interactions in interaction energies between cyclic peptide and water were measured and discussed.