Preferred Configurations of Peptide–Peptide Interactions

Abstract

The natural and fundamental proclivities of interaction between a pair of peptide units is examined using high-level ab initio calculations. The NH···O H-bonded structure is found to be the most stable configuration of the N-methylacetamide (NMA) model dimer, but only slightly more so than a stacked arrangement. The H-bonded geometry is destabilized by only a small amount if the NH group is lifted out of the plane of the proton-accepting amide. This out-of-plane motion is facilitated by a stabilizing charge transfer from the CO π bond to the NH σ* antibonding orbital. The parallel and anti-parallel stacked dimers are nearly equal in energy, both only slightly less stable than the NH···O H-bonded structure. Both are stabilized by a combination of CH···O H-bonding and a π→π* transfer between the two CO bonds.There are no minima on the surface that are associated with O lp →π*(CO) transfers, due in large part to strong electrostatic repulsion between the two O atoms which resists an approach of a carbonyl O from above the C=O bond of the other amide.

Analysis of Hydrogen Bonds in Crystals

“…Geometry optimization yielded a minimum which retains this H-bond, but this structure was 4.8 kcal/mol higher in energy than conformation I. A second possible starting point orients the two amide groups parallel to one another in a stacked arrangement, with no interamide H-bond, a structure which prior calculations have indicated might represent a minimum [100]. The minimum obtained for this structure was 6.0 kcal/mol higher in energy than I.…”

Predominant Information Quality Scheme for the Essential Amino Acids: An Information‐Theoretical Analysis

“…[58,59] Hydrogen bonding between the functional groups of the side chains of the protein also influences the geometry of the conformers along the protein. [60,61] Therefore all physicochemical properties also depend on these factors and it is very likely that ag iven property does not represent the amino acid characteristic, given its conformational diversity,a nd hence the property will not be adequate to characterize the amino acid within the protein. In contrast we www.chemphyschem.org speculate that information-theoretic measures are more suitable to characterize amino acids within the protein in spite of its conformational diversity.T his is because these measures grasp the essential features of the electron densities of systems.…”

The CH‥O H-Bond as a Determining Factor in Molecular Structure

“…The folding of the protein brings peptide groups from quite different segments of the backbone into close coincidence, so it is important to consider a fuller range of interpeptide geometries than the restricted low-energy sections of the (ϕ,ψ) space. A full search of the potential energy surface of a pair of CH 3 NHCOCH 3 (NMA) molecules was thus undertaken [168] so as to identify any minimum-energy structures, free of the restrictions imparted by a connecting unit.…”

“…4.5a unsurprisingly contained a strong NH··O HB [168]. This bond was able to achieve full strength since there was no peptide adjacent to the NH group whose carbonyl O could impede the approach of the carbonyl from the other NMA molecule.…”