Prediction Of Kinetic Parameters For Protein Folding

There are three main information sources of bioinformatics: sequence, structure and function. Protein folding problem focuses on the relationship between the sequence and the structure. Prediction of protein-folding kinetic parameters is a challenge in the protein folding problem.The significant correlation between protein folding rates and the sequence-predicted secondary structure suggests that folding rates are largely determined by the amino acid sequence. Here, we present a method for predicting the folding rates of proteins from sequences using the intrinsic properties of amino acids, which does not require any information on secondary structure prediction and structural topology. The contribution of residue to the folding rate is expressed by the residue'sΩvalue. For a given residue, itsΩdepends on the amino acid properties (amino acid flexibility and preference of the amino acid for secondary structures). Our investigation achieves 82% correlation with folding rates determined experimentally for simple, two-state proteins studied by now, suggesting that the amino acid sequence of a protein is an important determinant of the protein-folding rate and mechanism.We build a model of protein folding by introducing the concept of so-called"folding repulsive potential". Namely, we assume that there is the repulsive force between amino acid residue pairs in the protein molecule, which this force prevents the any two residues, which occur far apart in the amino acid sequence of the protein, come together in a contact. As the repulsive potential is increased the rate of folding is much slower because the folding barrier is increased. The potential is calculated by the Lennard-Jones-like and Morse-like formulas, respectively. For two-state proteins, multi-state proteins and short peptide, the results show that there are strong correlations between the potential and unfolding rate as well as Gibbs free energy of activation (correlation coefficients are more than 0.80), suggesting that inter-residue interaction is an important determinant of kinetic parameters of protein folding.Ramachandran plot helps to visualize the stereochemistry permissible value of protein dihedral angleΦandΨ. In Ramachandran plot, we consider the sum of distances between the point (Φ,Ψ) and the point (0, 0), and the distribution of secondary structure is ignored. Then, the correlation between the total distance and the rate constant of folding / unfolding or Gibbs free energy of activation is analyzed (correlation coefficients are also more than 0.80).