文摘
Protein structures are stabilized by multiple weak interactions, including the hydrophobic effect, hydrogen bonds, electrostatic effects, and van der Waals interactions. Among these interactions, the hydrogen bond is distinct in having its origins in electron delocalization. Recently, another type of electron delocalization, the n鈫捪€* interaction between carbonyl groups, has been shown to play a role in stabilizing protein structure. Here we examine the interplay between hydrogen bonding and n鈫捪€* interactions. To address this issue, we used data available from high-resolution protein crystal structures to interrogate asparagine side-chain oxygen atoms that are both acceptors of a hydrogen bond and donors of an n鈫捪€* interaction. Then we employed natural bond orbital analysis to determine the relative energetic contributions of the hydrogen bonds and n鈫捪€* interactions in these systems. We found that an n鈫捪€* interaction is worth 5鈥?5% of a hydrogen bond and that stronger hydrogen bonds tend to attenuate or obscure n鈫捪€* interactions. Conversely, weaker hydrogen bonds correlate with stronger n鈫捪€* interactions and demixing of the orbitals occupied by the oxygen lone pairs. Thus, these two interactions conspire to stabilize local backbone鈥搒ide-chain contacts, which argues for the inclusion of n鈫捪€* interactions in the inventory of non-covalent forces that contribute to protein stability and thus in force fields for biomolecular modeling.