These two authors contributed equally to this work.
QM/MM Study of Epitope Peptides Binding to HLA-A*0201: The Roles of Anchor Residues and Water
Article first published online: 20 OCT 2009
© 2009 John Wiley & Sons A/S
Chemical Biology & Drug Design
Volume 74, Issue 6, pages 611–618, December 2009
How to Cite
Li, Y., Yang, Y., He, P. and Yang, Q. (2009), QM/MM Study of Epitope Peptides Binding to HLA-A*0201: The Roles of Anchor Residues and Water. Chemical Biology & Drug Design, 74: 611–618. doi: 10.1111/j.1747-0285.2009.00896.x
- Issue published online: 28 OCT 2009
- Article first published online: 20 OCT 2009
- Received 18 June 2009, revised 8 August 2009 and accepted for publication 10 September 2009
- anchor residue;
A hybrid quantum mechanics/molecular mechanics scheme is described to explore the structural basis and energetic behavior of short peptide segments binding to HLA-A*0201. This method was used to analyze 50 structurally diverse non-americ peptides and results showed that the quantum mechanics/molecular mechanics-derived interaction energy, in conjugation with empirical desolvation free energy, linearly correlate well with the experimentally determined affinity. Further systematic investigations of several HLA-A*0201–peptide complexes confirmed the importance of anchor residues and water molecules in peptide binding, and quantitatively showed that: (i) the primary and second anchor residues provide a larger binding energy contribution (>3 kcal/mol) than the non-anchor residues (<2 kcal/mol), (ii) native hydrophobic anchor residues replaced by polar amino acids will lead to a significant destabilization for bound complexes (>4 kcal/mol), and (iii) water molecules contribute significantly to stabilization of the complexes (>8 kcal/mol). We believe that this work is helpful for elucidating the roles of anchor residues and water molecules in peptides recognized and bound by HLA-A*0201.