Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling?

Details Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling? Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling?

2002-12-04

arxiv.org/abs/cond-mat/0212105v2

Journal of Molecular Biology 326 (2003) 911-931

Physics

Condensed Matter

Statistical Mechanics

44 pages, 12 postscript figures, corrected typos (will appear on JMB)

Scientific paper

What energetic and solvation effects underlie the remarkable two-state thermodynamics and folding/unfolding kinetics of small single-domain proteins? To address this question, we investigate the folding and unfolding of a hierarchy of continuum Langevin dynamics models of chymotrypsin inhibitor 2. We find that residue-based additive G\=o-like contact energies, although native-centric, are by themselves insufficient for proteinlike calorimetric two-state cooperativity. Further native biases by local conformational preferences are necessary for proteinlike thermodynamics. Kinetically, however, even models with both contact and local native-centric energies do not produce simple two-state chevron plots. Thus a model protein's thermodynamic cooperativity is not sufficient for simple two-state kinetics. The models tested appear to have increasing internal friction with increasing native stability, leading to chevron rollovers that typify kinetics that are commonly referred to as non-two-state. The free energy profiles of these models are found to be sensitive to the choice of native contacts and the presumed spatial ranges of the contact interactions. Motivated by explicit-water considerations, we explore recent treatments of solvent granularity that incorporate desolvation free energy barriers into effective implicit-solvent intraprotein interactions. This additional feature reduces both folding and unfolding rates vis-\`a-vis that of the corresponding models without desolvation barriers, but the kinetics remain non-two-state. Taken together, our observations suggest that interaction mechanisms

Affiliated with

Also associated with

No associations

Rating

Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling? does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling?, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling? will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-702687