Stabilization and Destabilization of the C^δ−H···OC Hydrogen Bonds Involving Proline Residues in Helices

Abstract

There are a large number of helices in proteins that contain the Cδ−H···OC hydrogen bonds involving Pro. Ab initio and density functional methods at HF/6-31G*, B3LYP/6-31+G**, B3LYP/6-311+G**, and MP2/6-31+G** levels are used to determine the factors that may lead to the stabilization (destabilization) of these Cδ−H···OC hydrogen bonds. The calculations are performed for 16 helical models with their structures generated from the X-ray structures of proteins. The direct Cδ−H and OC interaction is not stabilizing for the cases where the Cδ−H···OC hydrogen bond immediately precedes a peptide hydrogen bond between (i+1)NH and (i−3)CO groups (here i is the Pro residue number). The direct Cδ−H and OC interaction is generally stabilizing for the cases where this peptide hydrogen bond is absent. Therefore, the formation of the (i+1)NH···(i−3)CO peptide hydrogen bond is likely to force the C−H and OC moieties into less favorable positions for the interaction. The strength of the Cδ−H···OC hydrogen bonds is significantly enhanced by cooperative hydrogen bonding involving the peptide hydrogen bonds in the helices and the capping interactions at the N-termini. The enhancement can be as large as 3−5 kcal/mol. The results suggest that the stability of the C−H···OC hydrogen bond depends on its environment, and this factor should be taken into consideration in the discussion of the energetic contribution of the C−H···OC hydrogen bonds to the stability.

A joint x-ray and neutron study on amicyanin reveals the role of protein dynamics in electron transfer

“…It is been shown that the strength of C-H⋯O bonds can be as high as 3-5 Kcal mol −1 depending on its environment and its strength could increase significantly by cooperative H bonding (31). The H-bonding analysis of amicyanin reveals that of the 39 H bonds present around 8 Å of copper site, only 8 of them are conventional whereas 31 of them are C-H⋯X hydrogen bonds (Figs.…”

QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3

“…9 The self-consistent charge density functional tight-binding method (SCC-DFTB) 10 and CHARMM force field 11 were used for the QM and MM atoms, respectively. Although high-level ab initio calculations (e.g., B3LYP/ 6-31G** or MP2/6-31G**) have been widely used for addressing these questions for chemical and biological systems, including the sys- tems with cooperative hydrogen bonding, 12 proton sponges, 13 polyacetylene, 14 and peptides with carbon hydrogen bonds, 15 these approaches are still too time-consuming for generating twodimensional free energy maps of enzyme-catalyzed reactions, as we did in this study. The SCC-DFTB approach has been used previously on a number of systems by us, and the results seem to be reasonable.…”

Observation of Weak CH⋅⋅⋅O Hydrogen Bonding to Unactivated Alkanes

“…In biological systems or molecular crystals, C À H···O hydrogen bonds are usually accompanied by other stronger molecular interactions that make it difficult to evaluate their relative contributions. Despite the importance of the CÀH···O hydrogen bond and extensive theoretical studies, [19][20][21][22][23][24][25] its nature is still being debated, [26][27][28][29] and there have been no experimental characterizations of its strength to date. We report here the first direct experimental observation of conformation changes induced solely by CÀH···O hydrogen bonding in a series of unactivated aliphatic carboxylate molecules, CH 3 (CH 2 ) n CO 2 À , in the gas phase, where the CÀH···O hydrogen bonding is the only molecular interaction driving the conformational changes.…”