Computer Modeling and NMR Studies of Interactions Between Phospholipids and Benzylamines

Abstract

An interactive receptor docking program has been implemented to facilitate computer modeling of the observed binding between N-alkylbenzylamines and phospholipid vesicles.The computer modeling studies indicate that the aromatic portion of the benzylamines lies in close proximity to the phospholipid ester alkyl chains while the N-alkyl groups may either project into the region occupied by the phospholipid head groups or fold back into the more hydrophobic environment. In this orientation, the interaction energies arising from a change in conformation with increasing N-alkyl hydrophobicity correlate very well with experimental observations. This hypothesis was validated by NMR experiments in which two-dimensional transferred nuclear Overhauser effects demonstrated that benzylamine N-alkyl chains longer than five carbons bind in a folded conformation.