Translocation of a cone-shaped HIV-1capsid through the nuclear pore complex

In recent experiments, it has been observed that an intact cone-shaped HIV-1 capsid translocates through the nuclear pore complex (NPC) before the capsid disassembly within the host cell nucleus. Capsid translocation through NPC raises numerous concerns, such as how the capsid overcomes the nuclear protein (also called nup) created barrier within the pore. And since the HIV-1 capsid has a cone shape with a narrow tip and a broad back, will translocation be advantageous if the capsid enters the pore through a narrow end? We develop an analytical model for transporting viral cone-shaped HIV-1 capsid through the NPC, focusing on the energy barrier created by nups within the pore and the energy contribution of capsid-nup interaction to reduce the barrier. We analyze the system's free energy profile as capsid translocates along the pore. Derive the capsid's translocation probability for reaching the trans end of the pore. The results show how the capsid's translocation through NPC is more favorable if it enters through the narrow end rather than the wide end. Also, with the strength of the capsid-nup interaction, the capsid's probability of reaching the nucleus increases, and the translocation process fastens. At last, we propose an optimized shape of cargo for successful translocation through the nanopore.