MOLECULAR SIMULATION OF PEPTIDE INTERACTIONS WITH AN RP-HPLC SORBENT

A simulation procedure based on molecular dynamics has been developed for modeling the interaction of peptides with n-alkylsilica reversed p hase chromatographic sorbents. A four-step docking procedure was used which included the following stages: (1) interactive rigid-body dockin g of the peptide with an n-butylsilica sorbent using amino acid hydrop hobicity coefficients to direct the orientation; (2) automated rigid-b ody docking by a Monte Carlo simulated annealing procedure in the spac e of six orientational parameters; (3) solvation of the peptide-sorben t complex with water, and (4) automated docking by molecular dynamics simulated annealing in the full Cartesian coordinate space. The proced ure has been validated with the simulation of the binding of the pepti de bombesin to an n-butylsilica C4 sorbent. The results were analyzed in terms of the change in conformation of both the n-butyl ligand chai ns and the peptide solute following peptide docking. These studies dem onstrate that the partial helical character of bombesin was maintained throughout the high-temperature annealing, Overall, this investigatio n demonstrates the potential of molecular dynamics procedures to aid i n the elucidation of peptide interactions with immobilized hydrophobic ligands. Moreover, this study provides a systematic approach to inves tigate the potential role of hydrophobic effects in peptide-surface in teractions.