Theoretical calculations on cyclohexaglycine and three-dimensional derivatives. conformational analysis and calculations of host-guest properties of peptides

Abstract

Molecular modelling studies combining computer graphics, molecular mechanics and molecular dynamics calculations are reported for some peptide systems. Conformation analyses have been carried out for cyclohexaglycine and two basket-like three-dimensional derivatives, and some preliminary calculations have been carried out to investigate their properties as binding agents with another peptide molecule N-acetyl- l-alanine ( N-Ac-L-Ala). After an exhaustive conformational search on the cyclohexaglycine, several features involved in the recognition properties displayed by these compounds were analysed: the conformational preferences of the free and complexed receptors, binding affinity, nature and orientation of binding sites and the macro(poly)cyclic effect. There are considerable changes in the cyclohexaglycine conformation when it is either inserted in a three-dimensional structure or when it interacts with other peptide molecules, thus simulating protein structures. The dual features of the flexibility and/or the rigidity of the ligands must be taken into account in order to gain an understanding of molecular recognition. In addition to hydrogen bonding effects, we found that electrostatic and hydrophobic interactions play an important role in the molecular recognition of neutral molecules.