Paper Citing NAMD - Abstract
Stavrakoudis, Athanassios
Computational modelling and molecular dynamics simulations of a cyclic peptide mimotope of the CD52 antigen complexed with CAMPATH-1H antibody
MOLECULAR SIMULATION, 36:127-137, 2010
A peptide mimotope of the CD52 antigen with the sequence T(1)SSPSAD(7) has been co-crystallised with the CAMPATH-1H antibody. Molecular dynamics (MD) simulations in explicit water of the T(1)SSPSAD(7) peptide in both antibody free and bound states showed that the peptide's beta-turn remained stable in the bound state but it was eliminated in the free state. Based on the observation that Thr(1) and Ala(6) residues made close contacts through their side chain, a new peptide mimotope is proposed: (S,S)-C(1)SSPSCD(7). Thr(1) and Ala(6) residues have been mutated in Cys residues and a disulphide bond has been imposed. The new analogue has been simulated in both antibody bound and free states with MD in explicit water. It was found that the peptide remained in the stable beta-turn conformation, both in complexed and free states. The difference in configurational entropy was estimated to be 0.15 kJ/K/mol. However, despite the structural similarity, the cyclic analogue lost more than 25% of its buried surface area contact with the antibody and a couple of critical hydrogen bond interactions were broken. It is concluded that design of cyclic analogues that mimic the bound conformation of peptides should be carefully performed and conformational `freezing' does not necessarily guarantee better binding.
