Studies Of Protein Folding Mechanism, Structural Splitting And Binding-site Diversity

There are three information sources of protein science in informatics: sequence, structure and function. The problem of protein folding belongs to the relationship between protein sequence and its structure; and the problem of relationship between protein structure and its biological function are one of the largest challenges in molecular biology.Structural determinants of protein-folding mechanism were studied. We assumed that there is a repulsive potential between amino acid residue pairs in protein structure. When protein folds, their conformation collapses. A residue lies close to another residue and so would cause steric hindrance to further fold. So the folding rate decreased quickly with an increasing magnitude of the repulsive barrier.Two different mathematical formulas were used to describe the potential function. One is an equation based on Lennard-Jones formula, which the potential is inversely proportional to residue distance to the 6.5-th power (E = 1/d^6.5). The other is similar to Morse formula and the potential decreased exponentially with increase in the distance (E = e^-1.56×d). 66 two-state proteins, multistate proteins and short peptide were analyzed statistically. The result shows a strong correlation between the potentials and folding rates, which correlation coefficient are 0.80 and 0.81, respectively. Contact residues are the determinants of protein-folding kinetics.Protein structures, especially tertiary structures, are closely related to their biological roles. However, it is difficult to distinguish between secondary structure and tertiary one. Here, the backbone structure of a protein was suppressed the noise of high-frequency and folding pattern of low-frequency was reserved. This implies that secondary structure is removed from protein structure and"pure"tertiary structure is obtained. This approach highlights the long-range structure of protein and can provide a data source for prediction of protein structure.It is very difficult to superpose the spatial structures of proteins in study of the relationship between protein structures and their functions. We herein selected porphyrin-binding myoglobin proteins which are different in sequence and structure. The fit superposition of global structures of proteins was performed using ligand superposition. Structural diversity of a series of proteins is shown and provides necessary information for 3D-QSAR analysis.