ScholarWorks@숙명여자대학교

초록

The native structure of a protein is stabilized by a number of interactions such as main-chain hydrogen bonds and side-chain hydrophobic contacts. However, it has been challenging to determine how these interactions contribute to protein stability at single amino acid resolution. Here, we quantified site-specific thermodynamic stability at the molecular level to extend our understanding of the stabilizing forces in protein folding. We derived the free energy components of individual amino acid residues separately for the folding of the human Pin WW domain based on simulated structures. A further decomposition of the thermodynamic properties into contributions from backbone and side-chain groups enabled us to identify the critical residues in the secondary structure and hydrophobic core formation, without introducing physical modifications to the system as in site-directed mutagenesis methods. By relating the structural and thermodynamic changes upon folding for each residue, we find that the simultaneous formation of the backbone hydrogen bonds and side-chain contacts cooperatively stabilizes the folded structure. The identification of stabilizing interactions in a folding protein at atomic resolution will provide molecular insights into understanding the origin of the protein structure and into engineering a more stable protein. © 2021 American Chemical Society. All rights reserved.

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