The water factor in the protein-folding problem

Abstract

Globular proteins are produced as a linear chain of aminoacids in water solution in the cell and, in the same aqueous environment, fold into their respective unique and functional native structures. In spite of this, many theoretical studies have tried to explain the folding process in vacuum, but in this paper we adopt an alternative point of view: the folding problem of heteropolymers is analyzed from the solvent perspective. The thermodynamics of the folding process is discussed for a non homogeneous system composed by the chain and solvent together; hydrophobic effects, modulated by the polar/nonpolar attributes of the residue sequence and by its corresponding steric specificities, are proposed as basic ingredients for the mechanisms of the folding process. These ideas are incorporated in both lattice and off-lattice models and treated by Monte Carlo simulations. Configurational and thermodynamical results are compared with properties of real proteins. The results suggest that the folding problem of small globular protein can be considered as a process in which the mechanism to reach the native structure and the requirements for the globule stability are uncoupled.

Entropic formulation for the protein folding process: Hydrophobic stability correlates with folding rates

“…Besides in-depth support for some results already pointed out in our previous works [10,11,13,[15][16][17], one of our new results shows the existence of a strong correlation between the hydrophobic component of the protein stability and its folding rate.…”

The implications of gene heterozygosity for protein folding and protein turnover

“…One of the driving forces of the protein folding process is the hydrophobic effect (Anfinsen, 1973;Chandler, 2002;Rocha et al, 2004;Berne et al, 2009). Proteins contain a hydrophobic core of non-polar amino acids that interact weakly with water and are, consequently, driven into the interior of the protein (Nozaki and Tanford, 1971).…”

Effect of local thermal fluctuations on folding kinetics: A study from the perspective of nonextensive statistical mechanics

“…Part of such general properties may be better understood if one considers that the search mechanism is governed mainly by the hydrophobic effect, whose strength, as shown experimentally at least for small hydrophobic molecules [20,21], varies slightly in the temperature interval from about zero to 100 o C. Therefore, it is suggested that folding process should be composed of two temporal steps [22]: the search mechanism, as the first stage, followed by the overall stabilization that only begins with the chain close enough to its native conformation, when energy and structural requirements, as encoded in the residue sequence, would be associated in a productive and cooperative way.…”