Downhill, Ultrafast and Fast Folding Proteins Revised

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.

Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution

“…A review of proteins with diversified structures and biological activities, in terms of the increasing amount of information carried by a given protein and the degree of complexity of its structure, is discussed in detail in [ 22 , 23 ]. The summary of this analysis reveals the participation of the water environment in the construction of the quaternary structure.…”

“…In the present study, a model called the fuzzy oil drop (FOD) [ 22 ] was used to reveal the differentiation of solubility and predisposition to the formation of the fourth-order structure, as well as the interaction of the protein with the cell membrane. The arrangement of the hydrophobicity in accordance with the proposed model justifies the high solubility of downhill- and fast-folding proteins [ 22 ].…”

Multi-modal engineering ofBstDNA polymerase for thermostability in ultra-fast LAMP reactions

“…We and others have previously shown that thermal stability is a global property of a protein, and that amino acid changes throughout a protein's structure can lead to a higher melting temperature and performance at higher temperatures (40,41), and we therefore attempted to improve the function of Bst-LF at increasingly higher temperatures through several different, complementary mechanisms. The addition of the ultra-fast folding domain HP47 was anticipated to assist with formation of protein tertiary structure following translation (so-called 'assisted folding;' (42)(43)(44)) and improve the solubility of the enzyme for purification (43,45), but what was unanticipated was that HP47 might also allow the polymerase to better interact with DNA via its zwitterionic nature, and thereby improve the ability to carry out LAMP reactions. By further using machine-learning methods and supercharging we sought to further improve the stability and functionality of the enzyme in additive ways (46).…”

Contribution to the Understanding of Protein–Protein Interface and Ligand Binding Site Based on Hydrophobicity Distribution—Application to Ferredoxin I and II Cases

“…It should be noted that this classification of individual residues is not entirely new. Its first form has been proposed in [44] and modified versions were used throughout some of the other papers [32,59,60]. However, here we provide not only a formal definition with description of the calculation algorithm but also introduce some important improvements to use now on, hence its appearance in Results rather than in Methods.…”