Global Docking Of Flexible Peptide Segments To Recognize Interactions With Proteins

Peptide is critical to regulate the normal physiology function of the human body, therefore, performing a research on the mechanism of interaction between peptide and protein has extremely important theory significance and practical significance. At present, research means in structural biology are mainly realized by peptide-protein docking. Although the present docking method can predict some peptide-protein sites with partly known interaction information, there is no reliable method to predict those peptide-protein sites with completely unknown interaction information. Therefore, this paper proposed two creative method named blind systematic docking approach and SP (selection parameter) selection method in order to solve the above problem. The results showed that, almost all the selected examples through this method can finally predict optimal conformation (RMSD ～5.5 A with respect to the crystal structure) successfully. What’s more, through ISR-Affinity analysis, most of the results displayed in the largest ISR and Affinity region, which indicated that the prediction results through this method can meet the characteristic with high specificity and strong affinity.To apply this approach to drug design, we further studied on the drug development with HIV-1 peptide inhibitors as example, which was performed after two main process of blind systematic docking and interface design. The full-length peptide structure was created through Loop Modeling module, then on the basis of the peptide-protein interaction interface, we performed the interface design step. Calculated the energy value using Interface Score Function, then the reliable sequences from top 10% energy was finally received through PWM analysis. These final prediction results can be as the basis for the subsequent experimental research, and the prediction results may serve as new active peptide inhibitors against HIV-1.