000131105 001__ 131105
000131105 005__ 20240205173707.0
000131105 0247_ $$2doi$$a10.1002/pro.4905
000131105 0248_ $$2sideral$$a136756
000131105 037__ $$aART-2024-136756
000131105 041__ $$aeng
000131105 100__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan José$$uUniversidad de Zaragoza
000131105 245__ $$aEnergy, water, and protein folding: A molecular dynamics-based quantitative inventory of molecular interactions and forces that make proteins stable
000131105 260__ $$c2024
000131105 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131105 5203_ $$aProtein folding energetics can be determined experimentally on a case‐by‐case basis but it is not understood in sufficient detail to provide deep control in protein design. The fundamentals of protein stability have been outlined by calorimetry, protein engineering, and biophysical modeling, but these approaches still face great difficulty in elucidating the specific contributions of the intervening molecules and physical interactions. Recently, we have shown that the enthalpy and heat capacity changes associated to the protein folding reaction can be calculated within experimental error using molecular dynamics simulations of native protein structures and their corresponding unfolded ensembles. Analyzing in depth molecular dynamics simulations of four model proteins (CI2, barnase, SNase, and apoflavodoxin), we dissect here the energy contributions to ΔH (a key component of protein stability) made by the molecular players (polypeptide and solvent molecules) and physical interactions (electrostatic, van der Waals, and bonded) involved. Although the proteins analyzed differ in length, isoelectric point and fold class, their folding energetics is governed by the same quantitative pattern. Relative to the unfolded ensemble, the native conformations are enthalpically stabilized by comparable contributions from protein–protein and solvent–solvent interactions, and almost equally destabilized by interactions between protein and solvent molecules. The native protein surface seems to interact better with water than the unfolded one, but this is outweighed by the unfolded surface being larger. From the perspective of physical interactions, the native conformations are stabilized by van de Waals and Coulomb interactions and destabilized by conformational strain arising from bonded interactions. Also common to the four proteins, the sign of the heat capacity change is set by interactions between protein and solvent molecules or, from the alternative perspective, by Coulomb interactions.
000131105 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E45-23R$$9info:eu-repo/grantAgreement/ES/MICINN/PDC2021-121341-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-141068NB-I00
000131105 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000131105 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131105 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, Javier$$uUniversidad de Zaragoza
000131105 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000131105 773__ $$g33, 2 (2024), e4905 [24 pp.]$$pProtein sci.$$tProtein science$$x0961-8368
000131105 8564_ $$s12084075$$uhttps://zaguan.unizar.es/record/131105/files/texto_completo.pdf$$yVersión publicada
000131105 8564_ $$s2302901$$uhttps://zaguan.unizar.es/record/131105/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131105 909CO $$ooai:zaguan.unizar.es:131105$$particulos$$pdriver
000131105 951__ $$a2024-02-05-15:05:53
000131105 980__ $$aARTICLE