TY - JOUR

T1 - The Nature of the Enthalpy-Entropy Compensation and "Exotic" Arrhenius Parameters in the Denaturation Kinetics of Proteins

AU - Baklanov, Alexey V

AU - Kiselev, Vitaly G

N1 - Funding: This research was funded by the Russian Science Foundation, grant number 23-23-00275.

PY - 2023/6/25

Y1 - 2023/6/25

N2 - Protein unfolding is a ubiquitous process responsible for the loss of protein functionality (denaturation), which, in turn, can be accompanied by the death of cells and organisms. The nature of enthalpy-entropy compensation (EEC) in the kinetics of protein unfolding is a subject of debate. In order to investigate the nature of EEC, the "completely loose" transition state (TS) model has been applied to calculate the Arrhenius parameters for the unfolding of polyglycine dimers as a model process. The calculated Arrhenius parameters increase with increasing dimer length and demonstrate enthalpy-entropy compensation. It is shown that EEC results from the linear correlations of enthalpy and entropy of activation with dimer length, which are derived directly from the properties of the transition state. It is shown that EEC in solvated (hydrated, etc.) proteins is a direct consequence of EEC in proteins themselves. The suggested model allows us also to reproduce and explain "exotic" very high values of the pre-exponential factor measured for the proteins unfolding, which are drastically higher than those known for unimolecular reactions of organic molecules. A similar approach can be applied to analyzing the nature of EEC phenomena observed in other areas of chemistry.

AB - Protein unfolding is a ubiquitous process responsible for the loss of protein functionality (denaturation), which, in turn, can be accompanied by the death of cells and organisms. The nature of enthalpy-entropy compensation (EEC) in the kinetics of protein unfolding is a subject of debate. In order to investigate the nature of EEC, the "completely loose" transition state (TS) model has been applied to calculate the Arrhenius parameters for the unfolding of polyglycine dimers as a model process. The calculated Arrhenius parameters increase with increasing dimer length and demonstrate enthalpy-entropy compensation. It is shown that EEC results from the linear correlations of enthalpy and entropy of activation with dimer length, which are derived directly from the properties of the transition state. It is shown that EEC in solvated (hydrated, etc.) proteins is a direct consequence of EEC in proteins themselves. The suggested model allows us also to reproduce and explain "exotic" very high values of the pre-exponential factor measured for the proteins unfolding, which are drastically higher than those known for unimolecular reactions of organic molecules. A similar approach can be applied to analyzing the nature of EEC phenomena observed in other areas of chemistry.

KW - Entropy

KW - Kinetics

KW - Thermodynamics

KW - Proteins/chemistry

KW - Protein Unfolding

KW - Protein Denaturation

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85164846190&origin=inward&txGid=ab059b84b391be8f79dc04ab39c69ec2

UR - https://www.mendeley.com/catalogue/cf9f2d72-9a15-3136-859c-5f385da469d9/

U2 - 10.3390/ijms241310630

DO - 10.3390/ijms241310630

M3 - Article

C2 - 37445807

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 13

M1 - 10630

ER -