Indoles at interfaces: Calculations of electrostatic effects with density functional and molecular dynamics methods

Cation-pi interactions have been suggested as a key determinant of aromatic amino acid behavior. These interactions can be modeled as an electrostatic quadrupole moment from the atoms of the ring interacting with the environm ent. The preference of aromatic amino acids for the interface of membrane b ilayers has been suggested as an example of a cation-pi effect. Recently, m olecular dynamics simulations of indole and N-methylindole in an explicit P OPC (palmitoyl oleoyl phosphatidylcholine) membrane bilayer have been perfo rmed, using the CHARMM potential function. The CHARMM potential does not ex plicitly contain cation-pi interactions: The electrostatic model involves o nly point charges at the atomic centers. A proper interpretation of the mol ecular dynamics calculations requires an assessment of the accuracy of the electrostatic effects present in the CHARMM parameter set. The current stud y compares the electrostatic interaction energy from CHARMM with calculatio ns using the density functional program deMon. The calculations were perfor med for the case of a single point charge approaching indole along the x, y , or z directions. Additional calculations used snapshots from the molecula r dynamics trajectories of indole and N-methylindole to compare CHARMM and deMon electrostatic energies. The results suggest that much of the cation-p i interactions for indole is effectively included within the CHARMM potenti al function. (C) 1999 John Wiley & Sons, Inc.