Research On Relationship Of Protein Structure And Function Using Dynamical Correlation Network

The relationship between structure and function of biomacromolecule plays a key role in exploring the mechanism of the occurrence and development of diseases,researching and developing new drug.As more and more complicated regulation mechanisms of proteins have been raised,the conventional structural biological methods are insufficient to reveal these mechanisms.So molecular dynamics simulation has been widely used to supplement this shortage.Here,we introduced a novel dynamical correlation network method combining with the molecular dynamics simulation to explore the positive cooperation regulation mechanism of human acetylcholinesterase and the allosteric regulation mechanism of mutant K-Ras protein.Based on the confirmation of the previous work,we elucidated the regulation mechanisms of these two proteins in detail.According to the comparison of different systems,we can find that the dynamical correlation networks of proteins are significant different from those of inhibitor binding.At the same time,the efficient of information transfer will significantly change upon the binding of inhibitor.Finally,the regulation pathways were found with the shortest path algorithm and verified by the mutations of key residues and perturbation of dynamical networks.These results can improve the drug design targeted on these pathways.These two examples testified the importance of dynamical network method in the research of the long-range regulation mechanism of proteins related to diseases,which inspires a new idea for the research of regulation mechanism of other proteins.