Uncover the Mechanism of Nucleotide Import by HIV-1 Capsid

In this work, we carry out a series of Brownian diffusion simulations to elucidate the nucleotide importing process through the hexamer pores of HIV-1 capsid. Our simulations reveal the mechanism by which deoxynucleoside triphosphates (dNTPs) diffuse through the arginine ring, the role of electrostatic potential within the pore in the importing process, and surprisingly, how IP6s and ATPs, though competing with dNTPs for binding at the arginine ring, end up accelerating the nucleotide import rate by thousands of folds so that it is sufficiently high to fuel the encapsidated DNA synthesis.\n\nIMPORTANCEEfficient nucleotide import is critical to fuel the reverse DNA synthesis that takes place within the capsid. However, the mechanism by which capsid imports the nucleotides is presently unclear. The current study through Brownian simulations shed insights into the process. A clear understanding of the mechanism of nucleotide import can be informative in developing drugs that target the process.