Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

81-POS Board 34 An Investigation of the Effects of Model Simplification and Water Box Shell Size on the Molecular Dynamics Simulations of Peptide-loaded Major Histocompatibility Complex Proteins Onur Serçinoglu , Pemra Özbek. Marmara University, Istanbul, Turkey. Peptide-loaded Major Histocompatibility Complex (pMHC) proteins play a key role in the transmission of molecular signals through the immune system via their interaction with T-cell receptors. Many alleles and sub-types of these proteins are found to be associated with autoimmune diseases; hence the importance of understanding the mechanism of signal transduction within the complex is crucial. As a computational tool, molecular dynamics (MD) simulations is commonly used for this purpose, however the high number of alleles/subtypes as well as the considerably large size of the pMHC complex limits the usage of this method in a large-scale comparative study. In this regard, reducing the size of the system by neglecting certain domains of the complex or decreasing the solvation shell size are two options previously investigated by researchers to obtain a computationally more manageable system without significant loss in accuracy. In this work, we performed 5 ns duplicate simulations of Human Leukocyte Antigen HLA*B-27:05 and HLA*B-27:09 sub-types binding 3 different peptide epitopes with simplified/full complex and different shell sizes of 10 Å and 20 Å. Simplification was done by excluding the α-3 domain of the antigen and β2-microglobulin. The overall Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) profiles were compared for each simulation setup. Between the sub-types, no significant difference was observed in terms of RMSD and RMSF profiles. However, we observed a peptide detachment in one simulation of the HLA*B-27:05 allele binding a peptide derived from Cathepsin A (pCatA) in a simplified setup with 20 Å shell size. Our results indicate the importance of checking peptide binding in parallel simulations before proceeding with longer MD simulations.

134