Computer Modeling and NMR Studies of Interactions Between Phospholipids and Benzylamines

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.