Water as a conformational editor in protein folding.
As molecules approach one another in aqueous solution, desolvation free energy barriers to association are encountered. Experiments suggest these (de)solvation effects contribute to the free energy barriers separating the folded and unfolded states of protein molecules. To explore their influence on the energy landscapes of protein folding reactions, we have incorporated desolvation barriers into a semi-realistic, off-lattice protein model that uses a simplified physico-chemical force-field determined solely by the sequence of amino acids. Monte Carlo sampling techniques were used to study the effects on the thermodynamics and kinetics of folding of a number of systems, diverse in structure and sequence. In each case, desolvation barriers increase the stability of the native conformation and the cooperativity of the major folding/unfolding transition. The folding times of these systems are reduced significantly upon inclusion of desolvation barriers, demonstrating that the particulate nature of the solvent engenders a more defined route to the native fold.
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Richard B
RB
Sessions
Geraint L
GL
Thomas
Martin J
MJ
Parker
D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000378:metabolism*
D014867:Water