Monte Carlo Simulations of HIV Capsid Protein Homodimer

Abstract

Capsid protein (CA) is the building block of virus coats. To help understand how the HIV CA proteins self-organize into large assemblies of various shapes, here we aim to computationally evaluate the binding affinity and interfaces in a CA homodimer. We model the N-and C-terminal domains (NTD and CTD) of the CA as rigid bodies, and treat the five-residue loop between the two domains as a flexible linker. We adopt a transferrable residue-level coarse-grained energy function to describe the interactions between the protein domains. In seven extensive Monte Carlo simulations with different volumes, a large number of binding / unbinding transitions between the two CA proteins are observed, thus allowing a reliable estimation of the equilibrium probabilities for the dimeric vs. monomeric forms. The obtained dissociation constant for the CA homodimer

Parameter Optimization for Interaction between C-Terminal Domains of HIV-1 Capsid Protein

“…Similar to our previous study 36 of the full-length CA, we performed seven MC simulations for a pair of CTDs ( To identify the underlying reasons for the weak binding of the CTDs in the Kim-Hummer model, we analyzed the interaction energy when the two CTDs are in the desired binding pose as described by the experimental dimer structure. As mentioned in Methods, the total energy is the sum of the interaction energies between each pair of residues from different CTDs.…”

“…2 Simulations of isolated CTDs thus will not suffer the complications in our previous study 36 Because the binding interface in the dimer of isolated CTDs is essentially identical to those in the dimer of full-length CAs 2 and in the CA assemblies, our effort here is an important step toward developing a realistic structural model for simulating large CA assemblies.…”

“…For instance, some models have a helix-level resolution with each α-helix of the CA represented by a cylinder 28,34,35 or a few spheres, 30 while other models have a residue-level resolution with each residue represented by a bead. 29,32,36 The number of CG sites with attractive interactions also varies, ranging from a few per monomer 28−31,33−35 to one per residue. 32,36 Most of these CG models 28−31,33−35 follow an ad hoc approach, employing experimental CA complexes as the targets.…”

Multiscale Modeling of Hepatitis B Virus Capsid Assembly and its Dimorphism

“…[42, 43, 95–111]), and CG models based on protein structures have led to insights about specific virus assembly processes (e.g. [112–118]).…”

“…[42,43,[95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111]), and CG models based on protein structures have led to insights about specific virus assembly processes (e.g. [112][113][114][115][116][117][118]).…”