ABSTRACT
Objective To develop a novel computer method for identifying the critical amino acid residues in the receptor-ligand interactions. Methods GPIbα/vWF-A1 crystal structure was taken from Protein Data Bank (PDB code 1SQ0). Free molecular dynamics simulations were performed to observe the formation and evolution of hydrogen bonding and salt bridge on the binding sites of GPIbα and vWF-A1 by VMD. A residue interaction index, which was scored with the survival ratios of salt bridges and/or hydrogen bonds involved in interaction of a residue to other(s), was used as a criterion of the residue’s role in interaction between the receptor and ligand. Results In the interface, 21 residues in GPIbα and 21 residues in vWF-A1 were significantly identified to participate in the interaction between GPIbα and vWF-A1; 20 of these 42 key residues were verified by previous mutagenesis experiments. Conclusions This novel approach is useful for computationally identifying the key residues involved in GPIbα-vWF interaction, and has potential in developing new strategy for the traditional mutagenesis experiments and the antithrombotic mAbs drug design.