How Ligand Binding Affects the Dynamical Transition Temperature in Proteins

• Published in: Chemphyschem Vol. 21; no. 9; pp. 916 - 926
• Main Authors: Krah, Alexander, Huber, Roland G., Bond, Peter J.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 05.05.2020
• Subjects: Binding Sites; dynamical transition temperature; Glass transition temperature; hydrogen mean square displacement (MSD); ligand binding; Ligands; Molecular dynamics; molecular dynamics (MD) simulations; Molecular Dynamics Simulation; Protein Conformation; Proteins; Proteins - chemistry; Solvents - chemistry; Temperature; Temperature dependence; Thermodynamics; Transition Temperature; Water - chemistry; hydrogen mean square displacement (MSD); dynamical transition temperature; molecular dynamics (MD) simulations; proteins; ligand binding
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201901221

The biochemical functions of proteins are activated at the protein glass transition temperature, which has been proposed to be dependent upon protein‐water interactions. However, at the molecular level it is unclear how ligand binding to well‐defined binding sites can influence this transition temperature. We thus report molecular dynamics (MD) simulations of the ϵ subunit from thermophilic Bacillus PS3 in the ATP‐free and ligand‐bound states over a range of temperatures from 20 to 300 K, to study the influence of ligand association upon the transition temperature. We also measure the protein mean square displacement (MSD) in each state, which is well established as a means to quantify this dynamical temperature dependence. We find that the transition temperature is largely unaffected by ligand association, but the MSD beyond the transition temperature increases more rapidly in the ATP‐free state. Our data suggests that ligands can effectively “shield” a binding site from solvent, and hence stabilize protein domains with increasing temperature. Is the transition temperature dependent upon ligand binding? Molecular dynamics (MD) simulations show that association of ligand to a high affinity binding site does not induce a change in the transition temperature, where the protein becomes active. However, ligand binding causes a decreased flexibility after crossing the transition temperature.