J. Kolafa et al., Essential motions and energetic contributions of individual residues in a peptide bound to an SH3 domain, BIOPHYS J, 79(2), 2000, pp. 646-655
We have studied protein-ligand interactions by molecular dynamics simulatio
ns using software designed to exploit parallel computing architectures. The
trajectories were analyzed to extract the essential motions and to estimat
e the individual contributions of fragments of the ligand to overall bindin
g enthalpy. Two forms of the bound ligand are compared, one with the termin
i blocked by covalent derivatization, and one in the underivatized, zwitter
ionic form. The ends of the peptide tend to bind more loosely in the capped
form. We can observe significant motions in the bound ligand and distingui
sh between motions of the peptide backbone and of the side chains. This cou
ld be useful in designing ligands, which fit optimally to the binding prote
in. We show that it is possible to determine the different contributions of
each residue in a peptide to the enthalpy of binding. Proline is a major n
et contributor to binding enthalpy, in keeping with the known propensity fo
r this family of proteins to bind proline-rich peptides.