A Molecular Mechanics Study on the Intermolecular Association Complex of a Cyclic Hexapeptide with an Alkylamine

Abstract

The structure of cyclic hexapeptides, hexaglycine (c-Gly6) and that with two leucine residures (c-(LeuGlyGly)2), were estimated with molecular mechanics calculation (CAChe Mechanics, Fujitsu Co.) and CONFLEX (Conflex Co.). The most stable structures of c-Gly6, a pair of mirror images with each other, show a twisted oval feature with four pairs of intramolecular hydrogen bonds. Calculation for the c-(LeuGlyGly)2 was done with six initial structures, which were formulated by adding a pair of leucine branches to the c-Gly6 structures (three cases for each Gly6 structure). As a result, five different types of stable structures were afforded, all of which basically retained the original hexapeptide skeleton. The difference in total energies among the stable structures was less than 0.9 kcal/mol. One molecule of isobutylamine was added to one of the stable structures and calculation was made to afford stable structures for the 1:1 complex between c-(LeuGlyGly)2 and the amine. The resulting structure have the ring structure similar to the original hexaglycine ring. The stabilization energy for the 1:1 complex was calculated as -10.2 kcal/mol, with the van der Waals term as the major contribution.