Molecular Dynamics Simulations of HLA-CW4-β2M-KIR2DL1 Protein Complex with Peptide QYDDAVYKL

Abstract

Molecular dynamics (MD) simulation was used to study the interactions of two immune proteins of HLA-Cw4-β2m-KIR2DL1 complex with small peptide QYDDAVYKL (nine amino acids) in an aqueous solution. This study aims to gain detailed information about the conformational changes and the dynamics of the complex. The parameters and force field for performing the MD simulations needed to calibrate the complex structure were examined and identified. The non-bonded interactions (electrostatic and van der Waals contributions), H-bond formation, and salt bridges between the ligand HLA-Cw4 and the receptor KIR2DL1, were estimated using the obtained MD simulation. The surface area buried due to binding was calculated to get insight into the causes of the specificity of the receptor to the ligand and to explain the mutations experiment. The study concluded that β2-microglobulin, one part of the complex, is not directly interacting with the peptide at the groove; therefore, it could be neglected from simulation. Our results showed that β2-microglobulin does not have any significant effect on the dynamics of the 3D-structure of the complex. This project will help optimize candidate drug design, a small peptide that disrupts the interaction, for the optimal biological effect.