Downhill, Ultrafast and Fast Folding Proteins Revised.

Mateusz Banach,Leszek Konieczny,Katarzyna Stapor,Piotr Fabian,Irena Roterman

doi:10.3390/ijms21207632

Abstract

Research on the protein folding problem differentiates the protein folding process with respect to the duration of this process. The current structure encoded in sequence dogma seems to be clearly justified, especially in the case of proteins referred to as fast-folding, ultra-fast-folding or downhill. In the present work, an attempt to determine the characteristics of this group of proteins using fuzzy oil drop model is undertaken. According to the fuzzy oil drop model, a protein is a specific micelle composed of bi-polar molecules such as amino acids. Protein folding is regarded as a spherical micelle formation process. The presence of covalent peptide bonds between amino acids eliminates the possibility of free mutual arrangement of neighbors. An example would be the construction of co-micelles composed of more than one type of bipolar molecules. In the case of fast folding proteins, the amino acid sequence represents the optimal bipolarity system to generate a spherical micelle. In order to achieve the native form, it is enough to have an external force field provided by the water environment which directs the folding process towards the generation of a centric hydrophobic core. The influence of the external field can be expressed using the 3D Gaussian function which is a mathematical model of the folding process orientation towards the concentration of hydrophobic residues in the center with polar residues exposed on the surface. The set of proteins under study reveals a hydrophobicity distribution compatible with a 3D Gaussian distribution, taken as representing an idealized micelle-like distribution. The structure of the present hydrophobic core is also discussed in relation to the distribution of hydrophobic residues in a partially unfolded form.

Highlights

Despite many years of research [1], the mechanism of the protein folding process remains unresolved
The potential high rate of folding of the polypeptide chain was considered by evaluating the degree of generation of the hydrophobic core, in which the water environment was actively involved as the dominant factor
The hydrophobic core was regarded as an important factor stabilizing the tertiary structure

Summary

Introduction

Despite many years of research [1], the mechanism of the protein folding process remains unresolved. There are proteins with a small number of amino acids in the chain which are characterized by a very fast folding process. This group of proteins is known as fast-folding, ultrafast folding or downhill [2]. Another group of proteins are those that fold on their own, the participation of the ribosome is required [3]. An example of an extremely demanding process is the folding process which requires the participation of chaperones or chaperonins [4,5,6,7,8]

Methods

Results

Discussion

Conclusion