Coulombic and dispersive factors in the molecular recognition of peptides: PIXEL calculations on two NNQQ (Asn-Asn-Gln-Gln) crystal polymorphs.

The crystal-packing and cohesive energies in the structures of two polymorphs of the title tetrapeptide have been analyzed using molecule-molecule energies calculated using the PIXEL method. Coulombic energies are non-empirical and are much more accurate than those calculated using point-charge methods. The results explain and rationalize the cohesion and mutual recognition of these peptide molecules, with a clear distinction between polar and dispersive contributions, shedding light on subtle differences between polymorphic arrangements. For systems of the present size, the necessary calculations can be carried out on a personal computer and require quite acceptable computing times. Although an extension to larger peptides is problematic for obvious reasons, it is suggested that this type of analysis could be a valuable and practical tool in the understanding of the principles of peptide aggregation.