Temperature dependence of the free energy landscape of the src-SH3 protein domain.
The temperature dependence of the free energy landscape of the src-SH3 protein domain is investigated through fully atomic simulations in explicit solvent. Simulations are performed above and below the folding transition temperature, enabling an analysis of both protein folding and unfolding. The transition state for folding and unfolding, identified from the free energy surfaces, is found to be very similar, with structure in the central hydrophobic sheet and little structure throughout the rest of the protein. This is a result of a polarized folding (unfolding) mechanism involving early formation (late loss) of the central hydrophobic sheet at the transition state. Unfolding simulations map qualitatively well onto low-temperature free energy surfaces but appear, however, to miss important features observed in folding simulations. In particular, details of the folding mechanism involving the opening and closing of the hydrophobic core are not captured by unfolding simulations performed under strongly denaturing conditions. In addition, free energy surfaces at high temperatures do not display a desolvation barrier found at lower temperatures, involving the expulsion of water molecules from the hydrophobic core.
Guo
Weihua
W
Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
Lampoudi
Sotiria
S
Shea
Joan-Emma
JE
D003198:Computer Simulation; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011336:Probability; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry* / Q000378:metabolism
D012997:Solvents; D019061:src-Family Kinases