134
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.
