functional and structural insights revealed by molecular dynamics simulations of an essential rna editing ligase in trypanosoma brucei功能和结构的见解揭示了分子动力学模拟的一个重要rna编辑连接酶在锥虫属brucei.pdfVIP

Functional and Structural Insights Revealed by Molecular Dynamics Simulations of an Essential RNA Editing Ligase in Trypanosoma brucei 1 1 1,2,3,4 Rommie E. Amaro *, Robert V. Swift , J. Andrew McCammon 1 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America, 2 NSF Center for Theoretical Biological Physics (CTBP), University of California San Diego, La Jolla, California, United States of America, 3 Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America, 4 Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of America Abstract RNA editing ligase 1 (TbREL1) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high- resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD) simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1’s funct