Open AccessExperimentally determined strengths of favorable and unfavorable interactions of amide atoms involved in protein self-assembly in water
Author(s) -
Xian Cheng,
Irina A. Shkel,
Kevin O’Connor,
M. Thomas Record
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2012481117
Subject(s) - amide , chemistry , context (archaeology) , hydrogen bond , protein structure , crystallography , nitrogen , urea , chemical physics , biophysics , molecule , organic chemistry , biochemistry , biology , paleontology
Folding and other protein self-assembly processes are driven by favorable interactions between O, N, and C unified atoms of the polypeptide backbone and side chains. These processes are perturbed by solutes that interact with these atoms differently than water does. Amide NH···O=C hydrogen bonding and various π-system interactions have been better characterized structurally or by simulations than experimentally in water, and unfavorable interactions are relatively uncharacterized. To address this situation, we previously quantified interactions of alkyl ureas with amide and aromatic compounds, relative to interactions with water. Analysis yielded strengths of interaction of each alkylurea with unit areas of different hybridization states of unified O, N, and C atoms of amide and aromatic compounds. Here, by osmometry, we quantify interactions of 10 pairs of amides selected to complete this dataset. An analysis yields intrinsic strengths of six favorable and four unfavorable atom-atom interactions, expressed per unit area of each atom and relative to interactions with water. The most favorable interactions are sp 2 O-sp 2 C (lone pair-π, presumably n -π*), sp 2 C-sp 2 C (π-π and/or hydrophobic), sp 2 O-sp 2 N (hydrogen bonding) and sp 3 C-sp 2 C (CH-π and/or hydrophobic). Interactions of sp 3 C with itself (hydrophobic) and with sp 2 N are modestly favorable, while sp 2 N interactions with sp 2 N and with amide/aromatic sp 2 C are modestly unfavorable. Amide sp 2 O-sp 2 O interactions and sp 2 O-sp 3 C interactions are more unfavorable, indicating the preference of amide sp 2 O to interact with water. These intrinsic interaction strengths are used to predict interactions of amides with proteins and chemical effects of amides (including urea, N -ethylpyrrolidone [NEP], and polyvinylpyrrolidone [PVP]) on protein stability.