Noncovalent Carbon‐Bonding Interactions in Proteins

Abstract

Supportinginformation (including details of computational methods) and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Evaluating Unexpectedly Short Non-covalent Distances in X-ray Crystal Structures of Proteins with Electronic Structure Analysis

“…Beyond providing a foundation for atomistic understanding of the behavior of biomacromolecules, crystal structures also heavily influence computational chemistry through their use in experimental tuning and validation of molecular mechanics (MM) force field models, 1−4 in validation of higher-level, quantum mechanical (QM) methods, 5−7 and in the development of data-driven models. 8 The over 100 000 protein structures in the Protein Data Bank (PDB) 9 provide a rich source of information that has been heavily mined in recent years, typically in conjunction with QM simulation, to reveal previously unknown noncovalent interactions including non-covalent carbon bonds, 10,11 n-to-π* interactions, 12,13 protein−ligand cation−π, aromatic, or other interactions, 14−19 and to shed light on salt bridges. 20 Within the domain of hydrogen bonding in particular, PDB surveys have provided guidance on less well-known NH••• N, 21−23 sulfur-containing, 24−26 X−H π, 27,28 and CH•••O 29 hydrogen bonds, among others.…”

Versatility of the Cyano Group in Intermolecular Interactions

“…This same phenomenon occurs on a divalent chalcogen Y atom, but each of its two RY bonds leads to a separate σ-hole, and a logical extension provides three σ-holes around a Z pnicogen atom in its ZR 3 configuration. Recent works [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] have also included tetrel atoms T (C and Si, etc.) in this category, as the tetravalent TR 4 molecule has four σ-holes, so could, at least in principle, participate in as many as four simultaneous tetrel bonds.…”

When are two hydrogen bonds better than one? Accurate first-principles models explain the balance of hydrogen bond donors and acceptors found in proteins

“…Noncovalent interactions are ubiquitous in biological systems, playing essential roles in both enzyme catalysis 1 and the structural properties of both DNA 2 and proteins. [3][4][5][6] Over the years, an increasing array of interactions including noncovalent carbon bonds, 7,8 n to p* interactions, [9][10][11] protein-ligand cationp, aromatic, salt bridges, 12 and other interactions [13][14][15][16][17][18][19] have been studied to understand their potential roles in biomolecular structure and function. Among these, hydrogen bonds (HBs) are a particularly critical class of noncovalent interactions for biological function.…”