Abstract
The human sterile alpha motif SAM and HD domain-containing protein 1 (SAMHD1) restricts in non-cycling cells type the infection of a large range of retroviruses including HIV-1, reducing the intracellular pool concentration of deoxynucleoside triphosphates (dNTPs) required for the reverse transcription of the viral genome. The enzyme is in equilibrium between different forms depending on bound cofactors and substrate. In this work, two SAMHD1 three-dimensional models have been investigated through classical molecular dynamics simulation, to define the role of cofactors and metal ions in the association of the tetrameric active form. A detailed analysis of the inter-subunit interactions, taking place at the level of helix 13, indicates that removal of metal ions and cofactors induces an asymmetric loosening of the monomer–monomer interface leading to the formation of a loose tetramer where the two dimeric interfaces are weakened in different way.
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Cardamone, F., Iacovelli, F., Chillemi, G. et al. A molecular dynamics simulation study decodes the early stage of the disassembly process abolishing the human SAMHD1 function. J Comput Aided Mol Des 31, 497–505 (2017). https://doi.org/10.1007/s10822-017-0014-9
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DOI: https://doi.org/10.1007/s10822-017-0014-9