Computer Simulation Of The Interaction And Recognition Of Protein Dimers

Quantitatively describing the principle of protein-protein interactions and recognition in molecular level is the key point for understanding the relationship between structure and function of protein complexes and designing protein complexes, hi these interactions among proteins, electrostatic and hydrophobic interactions are the two most important ones, which let protein molecules bond systematically.The problem of the protein stability changed by solvent environment is in the limelight. Recently, there have been some significant advances in this direction, a fast and simple method is still not available for accurate prediction of experimental observation. To solve this problem, we used the formal charge model to study electrostatic interactions of protein complexes. And a fast and effective model for predicting the salt and pH dependent properties of protein complexes was presented here and applied to the analysis and prediction of the stability of protein structures. All simulations were performed on the native 2Zn insulin and its fast-acting mutants. It is found that the results agree well with experimental data.Binding free energy calculation is another focus of the study on protein-protein interactions and recognition. Although many methods have been developed to understand this problem for many years, most of them is still of some lacks. One problem is that the treatment of the conformational entropy is either simple to set to a constant, or still complicated to depend on the calculation of the probability of each rotamer. Our goal is to establish a simple and effective empirical approach to calculate the conformational entropy and the binding free energy by analysis ofJ:protein interface. Three variables of the binding interface information of 20 protein complexes, including the binding accessible number (Nb), hydrophilic pair (N^,) and apolar solvent-accessible surface areas (&ASAapol) are analyzed. It is found that Nbcorrelates very well (R = 0.97) with the loss of binding side-chain conformation entropy, and the binding free energy depends on Nb, Npair, and ASAapol, in which thefitting coefficient is 0.95. In addition, this model is applied to the docking program as an effective and fast target function. The results show that the score function of complexes is effective and simple for rational protein docking and its design.