Effect of finite size on cooperativity and rates of protein folding

Abstract

We analyze the dependence of cooperativity of the thermal denaturation transition and folding rates of globular proteins on the number of amino acid residues, $N$, using lattice models with side chains,off-lattice Go models and the available experimental data. A dimensionless measure of cooperativity, ${\Omega }_c$ ($0<{\Omega }_c<\infty$), scales as ${\Omega }_c\sim N^{\zeta }$. The results of simulations and the analysis of experimental data further confirm the earlier prediction that $\zeta$ is universal with $\zeta =1+\gamma$, where exponent $\gamma$ characterizes the susceptibility of a self-avoiding walk. This finding suggests that the structural characteristics in the denaturated state are manifested in the folding cooperativity at the transition temperature. The folding rates $k_F$ for the Go models and a dataset of 69 proteins can be fit using $k_F=k_F^0\exp (-c{N}^{\beta })$. Both $\beta =1/2$ and 2/3 provide a good fit of the data. We find that $k_F=k_F^0\exp (-c{N}^{1/2})$, with the average (over the dataset of proteins) $k_F^0\approx (0.2\mu s{)}^{-1}$ and $c\approx 1.1$, can be used to estimate folding rates to within an order of magnitude in most cases. The minimal models give identical $N$ dependence with $c\approx 1$. The prefactor for off-lattice Go models is nearly four orders of magnitude larger than the experimental value.

17 pages, 3 figures, 2 tables

References in corpus (2)

• Protein folding mediated by solvation: water expelling and formation of the hydrophobic core occurs after the structure collapse
• Folding of the Protein Domain hbSBD

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