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

Source: [Solvation Effects and Driving Forces for Protein Thermodynamic And Kinetic Cooperativity: How Adequate Is Native-Centric Topological Modeling?](<https://www.sota2.com/research/paper/68fa1e4a7a2b558e293216cf>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2025-10-23T17:06:32.971Z

Authors: Huseyin Kaya, Hue Sun Chan

Published: 2002-12-04T20:39:01.000Z

## Abstract

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

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/cond-mat/0212105>)

[PDF](<https://arxiv.org/pdf/cond-mat/0212105.pdf>)