How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

Anna Glyakina,Oxana Galzitskaya

doi:10.3390/biom10020197

Abstract

The correlations between the logarithm of the unfolding rate of 108 proteins and their structural parameters were calculated. We showed that there is a good correlation between the logarithm of folding and unfolding rates (0.79) and protein stability and unfolding rate (0.79). Thus, the faster the protein folds, the faster it unfolds. Folding and unfolding rates are higher for the proteins with two-state kinetics, in comparison with the proteins with multi-state kinetics. At the same time, two-state bacterial proteins folds and unfolds two orders of magnitude faster than two-state eukaryotic proteins, and multi-state bacterial proteins folds and unfolds slower than multi-state eukaryotic proteins. Despite the fact that the folding rates of thermophilic and mesophilic proteins are close, the unfolding rates of thermophilic proteins is about two orders of magnitude lower than for mesophilic proteins. The correlation between unfolding rate and stability of thermophilic proteins is high (0.90). We also found that the unfolding rate correlates with such structural parameters as: size of the protein, radius of the cross-section, logarithm of absolute contact order, and radius of gyration. This information will be useful for engineering and designing new proteins with desired properties.

Highlights

In 1998, a relative contact order parameter was suggested, which is the average distance along the sequence between all pairs of contacting residues, normalized to the size of the protein
It was demonstrated that Vasa/solvent accessible surface (Sasa) correlates good with the logarithm of the folding rate [16]
We have previously shown that bacterial proteins with two-state kinetics fold and unfold faster than two-state eukaryotic proteins [23]

Summary

Introduction

The problem of predicting folding rates (kf ) for proteins with two-state and multi-state kinetics is still important and extensively studied [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. In 1998, a relative contact order (rCO) parameter was suggested, which is the average distance along the sequence between all pairs of contacting residues, normalized to the size of the protein (number of amino acid residues, further protein length). It was shown that the rCO correlates well (correlation coefficient is 0.81) with the logarithm of the folding rate for 12 two-state proteins [2]. Subsequent studies have shown that there is no correlation between rCO and logarithm of the folding rate of proteins [6,7,16]. It was found that the structural parameters, depending on the protein length (L), correlated well with the logarithm of the folding rate [16]. Α-structural proteins are less compact and the most rapidly folding proteins, while α/β-structural proteins are the most compact and the most slowly folding proteins [15]

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