Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations

[摘要] SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.

[发布机构] Department of Physics, Indian Institute of Technology Guwahati, Guwahati; Assam; 781039, India^1;Department of Biochemistry, MSC 7760, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio; TX; 78229-3900, United States^2

[效力级别] 计算机科学 [学科分类] 计算机科学（综合）

[关键词] Allosteric activation;Allosteric site;Cellular enzymes;HIV-1 infections;Molecular dynamics simulations;Myeloid cells;Reverse transcription;Tetrameric complex