Secondary Forces in Protein Folding

Abstract

A complete inventory of the forces governing protein folding is critical for productive protein modeling, including structure prediction and de novo design, as well as understanding protein misfolding diseases of clinical significance. The dominant contributors to protein folding include the hydrophobic effect and conventional hydrogen bonding, along with Coulombic interactions and van der Waals interactions. Over the past few decades, important additional contributors have been identified, including C-H•••O hydrogen bonding, n→π* interactions, C5 hydrogen bonding, chalcogen bonding, and interactions involving aromatic rings (cation-π, X-H•••π, π-π, anion-π, and sulfur-arene). These secondary contributions fall into two general classes: (1) weak but abundant interactions of the protein main chain, and (2) strong but less frequent interactions involving protein side chains. Though interactions with high individual energies play important roles in specifying nonlocal molecular contacts and ligand binding, we estimate that weak but abundant interactions are likely to make greater overall contributions to protein folding, particularly at the level of secondary structure. Further research is likely to illuminate additional roles of these noncanonical interactions and could also reveal contributions yet unknown.

Abiotic Hydrolysis Kinetics of N‐Acyl‐L‐homoserine Lactones: Natural Silencing of Bacterial Quorum Sensing Signals

“…This long‐range interaction, though, seems unlikely given that terminal electrons would likely stay situated around their respective nuclei. Newberry and Raines suggested an alternative explanation for chain‐composition dependent hydrolysis rates . AHLs can assume a geometry such that the non‐bonding orbital ( n ) of the amide oxygen inserts into the π* of the lactone, structurally analogous to proline (see Figure ).…”

Conformation control through concurrent N–H⋯S and N–H⋯OC hydrogen bonding and hyperconjugation effects

“…1), [13][14][15] or C-H/O interactions, 16,17 as well as phenomena such as n / p* hyperconjugative interactions, 18 Cbonds, 19 cation-p interactions, 20,21 and others. 22 Reports of non-covalent interactions in proteins which specically implicate the side-chain heteroatom of sulfurcontaining residues are rare and do not involve H-bonds; rather, they take the form of sulfur-aromatic interactions 23,24 or chalcogen bonds. 25 Studies on small peptide systems have revealed that backbone-backbone H-bonding interactions may exist in thioamides.…”

Comparison of the structure and function of a chimeric peptide modified titanium surface

“…Therefore, the antimicrobial effect of chimeric peptide is not directly proportional to its length and number of structural groups, and there is a certain relationship between its function and the number of functional groups in microenvironment. 39,40 XPS analysis of the binding elements' compositions of the Ti surface conrmed the presence of C 1s, O 1s (531.18 eV), Na 1s (1071.83 eV), P 2p (133.19 eV), C l2p (198.69 eV), and Ti 2p 3 (458.30 eV) as the chief components, as shown in Fig. 3.…”