PEPTIDE MODELS .14. AB-INITIO STUDY ON THE ROLE OF SIDE-CHAIN BACKBONE INTERACTION STABILIZING THE BUILDING UNIT OF RIGHT-HANDED AND LEFT-HANDED HELICES IN PEPTIDES AND PROTEINS

Previous ab initio computations revealed that the conformational build ing unit of the right-handed helix (phi approximate to -54 degrees, ps i approximate to -45 degrees) is not an energy minimum on two-dimensio nal-type Ramachandran potential energy surfaces (E = E{phi, psi}). The oretical investigations were performed on several single-amino-acid di amides such as For-Gly-NH2, For-L-Ala-NH2, Ac-L-Ala-NHMe, and For-L-Va l-NH2 containing amino acid residues (e.g., Ala) which can often be fo und in helices as shown by X-ray data analysis of globular proteins. T he current ab initio [self-consistent field (SCF)] results (based on f our different basis sets [3-21G, 4-21G, 4-21G, and 6-31G*]) presented point toward an intrinsic (i.e., non-environmental-assisted) stabilit y of the right-handed helical subconformation of a simple amino acid d iamide if the residue contains a polar side chain. Such is the case fo r a serine derivative when its -CH2OH side chain is favorably oriented . For the For-L-Ser-NH2 model compound two slightly different right-ha nded helical backbone conformations were determined. Depending on the relative orientation of the side chain, the conformational monomer of the 3(10) helix (a sharper helical structure with an [i, i + 3]-type H -bond network) as well as the building block of the ''standard'' alpha -helix (the regular helical structure with an [i, i + 4]-type H-bond n etwork) were determined computationally by geometry optimization. (C) 1997 John Wiley & Sons, Inc.