Energetics of hydrogen bonds in peptides

Abstract

Hydrogen bonds and their relative strengths in proteins are of importance for understanding protein structure and protein motions. The correct strength of such hydrogen bonds is experimentally known to vary greatly from Ϸ5-6 kcal͞mol for the isolated bond to Ϸ0.5-1.5 kcal͞mol for proteins in solution. To estimate these bond strengths, here we suggest a direct novel kinetic procedure. This analyzes the timing of the trajectories of a properly averaged dynamic ensemble. Here we study the observed rupture of these hydrogen bonds in a molecular dynamics calculation as an alternative to using thermodynamics. This calculation is performed for the isolated system and contrasted with results for water. We find that the activation energy for the rupture of the hydrogen bond in a ␤-sheet under isolated conditions is 4.76 kcal͞mol, and the activation energy is 1.58 kcal͞mol for the same ␤-sheet in water. These results are in excellent agreement with observations and suggest that such a direct calculation can be useful for the prediction of hydrogen bond strengths in various environments of interest.T he strength of the hydrogen bond in the linking of protein structures particular in a water environment is of essential importance to predict the activity of proteins such as enzyme action, protein folding, binding of proteins, and many other processes (1, 2). Although much has been written on protein dynamics in water (3), a detailed energy calculation including the correct water environment has been difficult to put into a computational framework. The energetics of hydrogen bonds within proteins is known to undergo large changes in water. The effect of water is also process dependent, so it is different here from protein signal transport (4). Such environmental changes in a hydrogen bond strength are important to the understanding of protein interactions, including drug design (5, 6). The drugreceptor hydrogen bond is operative in many applications (7).Hydrogen bonds are one of the major structural determinants, controlling active configurations by connecting protein structure in a fluxional equilibrium. The making and breaking of hydrogen bonds profoundly affects the rates and dynamic equilibria, which are responsible for much of the biological activity of proteins. This behavior is strongly medium dependent, so the action of these hydrogen bonds in isolated systems is quite different from the action in a water environment. The complex environment presented to the hydrogen bond by water is not easy to incorporate in calculations, but it is of major relevance, and results obtained need to be checked against experiments. A huge and complex phase space contributes to the effects of entropy on the hydrogen bond, particularly in water, and thus influences the free energy of these bonds. The general task of assessing the entropic contributions to the dynamic strength of these bonds is a matter of extensive research (8) and is difficult to quantify. Furthermore, it must be recognized that various relevant bonding environments will...

Nanomechanical strength mechanisms of hierarchical biological materials and tissues

“…This analysis provides additional proof that in the SDM three HBs rupture simultaneously, within less than 20 ps time scale. We note that it was reported in the literature that the time for HB breaking is of approximately 20 -40 ps (Sheu et al 2003), clearly supporting the notion that these HBs rupture simultaneously.…”

“…We note that the bond breaking energy E 0 b of a HB in water ranges from 3 to 6 kcal/mol (Sheu et al 2003), providing reasonable agreement with the computational results.…”

“…The observation of the change of mechanism from the FDM to the SDM regime enables us to actually extrapolate estimates of the unfolding forces from MD simulation speeds, approaching the pulling speeds used in experiment [the predicted unfolding forces at 1E 2 7 m/s are approximately 100 pN ]. (Sheu et al 2003). Thus, these snapshots strongly support the concept of cooperative bond rupture in the SDM.…”

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-β supramolecular networks

“…[53,57] However, residues in A1 microfibers ( Figure 6D) exhibit even higher protection factors. These observations suggest that the presence of Pro allows the cross β-structure packing to relax by extending the hydrogen bond lengths, [84] possibly preventing premature aggregation and in turn ensuring further assembly of the supramolecular network, which could be consistent with the higher amount of β-sheet content predicted by MD simulations for the Pro-containing A2 peptide at equilibrium. However this assumption remains to be confirmed through further structural analysis of the peptides.…”

Estimating Hydrogen Bond Energy in Integral Membrane Chromoproteins by High Hydrostatic Pressure Optical Spectroscopy

“…Single H-bond energies in proteins between 2 and 25 kJ/mol (167-2090 cm -1 ) have been reported (Sheu, Yang et al 2003;Wendler, Thar et al 2010), depending on the H-bond donor and acceptor as well as their environment. Most of the transition midpoint energies, Table 2 reveals several notable details about the free energy change related to breakage of the H-bonds in the LH2 complexes: (i) its value for isolated complexes is greater than for membrane/glycerolenchanced membrane complexes; (ii) it is greater in complexes with native carotenoid background (wt and B850-only) than in complexes, which contain neurosporene (neuro and B850+neuro); (iii) irrespective of the sample, its value in membrane/ glycerol-enhanced membrane complexes is similar (≤19 kJ/mol).…”