Study On Interaction Mechanism Between Sp1 And Two Kinds Of Histone Modification Enzyme Based On Molecular Simulation

In the past half century,they have become the main method of biological macromolecular structure and function research,which are homology modeling,molecular dynamics simulation and molecular docking molecular simulation technology.Among them,molecular simulation has been developed as a set of mature theory and method.The homology modeling technique can obtain the protein crystal structure under the condition of not a biological experiment.Molecular dynamics and molecular docking techniques can show the movement details of biological molecules with time.And the movement details can provide an analytical approach to the physical mechanism of the biomolecule interaction.The transcription factor Sp1,also known as specificity protein 1,has three zinc finger domains that binds to GC-rich motifs of many promoters.The encoded protein is involved in many cellular processes,including cell differentiation,cell growth,apoptosis,immune responses,response to DNA damage,and chromatin remodeling.Histone acetylation 1 and histone acetyltransferase p300 are a pair of mutual antagonistic histone modification enzyme.Both enzymes can bind to Sp1 zinc finger domains to suppress or promote the Sp1 biological activity.Sp1?HDAC1 and p300 regulate the expression of gene in human cells,and associate with the cause and evolution of many tumors.In this paper,we study the physical interaction mechanism of the transcription factor Spl(AA613?778)with two histone modification enzymes of HDAC1 and p300(AA1287?1713).First,we build the three-dimensional structures of molecules with homology modeling and optimize and perform 100ns molecular dynamics(MD)simulations after optimized and evaluated the structures.In the MD results,we found that the structure of Spl is instability and varied.In the analysis of molecular docking results,we found that to HDAC1 p300 is more stable in binding to Sp1.The interactions on binding surface of HD AC 1 to Spl and p300 to Spl are hydrogen-bonding interaction mainly and Pi-Pi interactions lesser.