Solvation free energy in governing equations for DNA hybridization, protein–ligand binding, and protein folding

Autor: Caroline Harmon, Austin Bui, Jasmin M. Espejo, Marc Gancayco, Jennifer M. Le, Juan Rangel, Daryl K. Eggers
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: FEBS Open Bio, Vol 14, Iss 11, Pp 1837-1850 (2024)
Druh dokumentu: article
ISSN: 2211-5463
DOI: 10.1002/2211-5463.13897
Popis: This work examines the thermodynamics of model biomolecular interactions using a governing equation that accounts for the participation of bulk water in the equilibria. In the first example, the binding affinities of two DNA duplexes, one of nine and one of 10 base pairs in length, are measured and characterized by isothermal titration calorimetry (ITC) as a function of concentration. The results indicate that the change in solvation free energy that accompanies duplex formation (ΔGS) is large and unfavorable. The duplex with the larger number of G:C pairings yields the largest change in solvation free energy, ΔGS = +460 kcal·mol−1per base pair at 25 °C. A van't Hoff analysis of the data is complicated by the varying degree of intramolecular base stacking within each DNA strand as a function of temperature. A modeling study reveals how the solvation free energy alters the output of a typical ITC experiment and leads to a good, though misleading, fit to the classical equilibrium equation. The same thermodynamic framework is applied to a model protein–ligand interaction, the binding of ribonuclease A with the nucleotide inhibitor 3′‐UMP, and to a conformational equilibrium, the change in tertiary structure of α‐lactalbumin in molar guanidinium chloride solutions. The ribonuclease study yields a value of ΔGS = +160 kcal·mol−1, whereas the folding equilibrium yields ΔGS ≈ 0, an apparent characteristic of hydrophobic interactions. These examples provide insight on the role of solvation energy in binding equilibria and suggest a pivot in the fundamental application of thermodynamics to solution chemistry.
Databáze: Directory of Open Access Journals
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