a computational analysis of atp binding of sv40 large tumor antigen helicase motoratp结合的计算分析sv40大肿瘤抗原解旋酶马达.pdfVIP

A Computational Analysis of ATP Binding of SV40 Large Tumor Antigen Helicase Motor 1 2 1 3,4 1,2 Yemin Shi , Hanbin Liu , Dahai Gai , Jianpeng Ma , Xiaojiang S. Chen * 1 Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America, 2 Chemistry Department, University of Southern California, Los Angeles, California, United States of America, 3 Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Bioengineering, Rice University, Houston, Texas, United States of America Abstract Simian Virus 40 Large Tumor Antigen (LTag) is an efficient helicase motor that unwinds and translocates DNA. The DNA unwinding and translocation of LTag is powered by ATP binding and hydrolysis at the nucleotide pocket between two adjacent subunits of an LTag hexamer. Based on the set of high-resolution hexameric structures of LTag helicase in different nucleotide binding states, we simulated a conformational transition pathway of the ATP binding process using the targeted molecular dynamics method and calculated the corresponding energy profile using the linear response approximation (LRA) version of the semi-macroscopic Protein Dipoles Langevin Dipoles method (PDLD/S). The simulation results suggest a three- step process for the ATP binding from the initial interaction to the final tight binding at the nucleotide pocket, in which ATP is eventually ‘‘locked’’ by three pairs of charge-charge interactions across the pocket. Such a ‘‘cross-locking’’ ATP binding process is similar to the binding zipper model reported for the F1-ATPase hexameric motor. The simulation also shows a