RETROMODIFIED RESIDUES - SMALL PEPTIDES AND POLYMERS - INTERACTIONS, FORCE-FIELD PARAMETRIZATION AND CONFORMATIONAL-ANALYSES

Suitable parameters for describing the conformational behavior of bis(acetamide) and malonamide retro-amide residues are obtained and tested. For this purpose, bonded parameters, i.e. stretching, bending, and torsion, were computed with the PAPQMD (program for approximate parametrization from quantum mechanical data) strategy and compared with experimentally derived force-field parameters for residues without retro-amide link. Electrostatic parameters were determined by fitting the Coulombic monopole-monopole electrostatic potential to the quantum mechanical electrostatic potential computed from both ab initio 6-31G(*) and semiempirical MNDO wave functions. In addition, the variation of the atomic charges with the conformation was investigated. Equilibrium geometries and thermodynamic properties for bis(acetamido)methane and N,N'-dimethylmalonamide obtained from molecular mechanical calculations using the derived parameters were compared with available experimental and quantum mechanical data. The selected parameters were then applied to the study of (i) the retro-dipeptides bis(acetamido)ethane and bis(acetamido)propane and (ii) the crystalline structure of several aliphatic polyamides. The conformational trends obtained for bis(acetamido)ethane and bis(acetamido)propane using ab initio and semiempirical quantum mechanical methods are in good agreement with the molecular mechanical results. Moreover, the minimal energy structures for nylon 1,3 and 1,5 on a solid-state model allowed us to explain the X-ray-refined data using the least-atom-linked-squares methods.