Modeling HIV-1 viral capsid nucleation by dynamical systems

Sadre-Marandi, Farrah; Liu, Yuewu; Liu, Jiangguo; Tavener, Simon; Zou, Xiufen

doi:10.1016/j.mbs.2015.10.007

Cited by 7 publications

(11 citation statements)

References 41 publications

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“…Assembly was strongly linked to protein concentration, and there was clearly a threshold protein concentration below which assembly did not occur. The existence of a critical protein concentration suggests that tube formation is a nucleated process, in accord with simple theories of helical polymerization 72,73 , and prior experimental 19,52,59,74 and theoretical [75][76][77] studies of orthoretroviral CA assembly.…”

Section: Rsv Ca Tube Assembly Is Strongly Dependent On Temperature Psupporting

confidence: 68%

In vitroassembly of the Rous Sarcoma Virus capsid protein into hexamer tubes under physiological conditions

Jaballah

Bailey

Desfosses

et al. 2017

Preprint

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During a proteolytically-driven maturation process, the ortho-retroviral capsid protein (CA) assembles to form the convex shell that surrounds the viral genome. In some orthoretroviruses, including Rous Sarcoma Virus (RSV), CA carries a short and hydrophobic spacer peptide (SP) at its C-terminus early in the maturation process, which is progressively removed as maturation proceeds. In this work, we show that RSV CA assembles in vitro at physiological temperatures, forming hexamer tubes that effectively model the mature capsid surface. Tube assembly is strongly influenced by electrostatic effects, and is a nucleated process that remains thermodynamically favored at lower temperatures, but is effectively arrested by the large Gibbs energy barrier associated with nucleation.

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Section: Rsv Ca Tube Assembly Is Strongly Dependent On Temperature Psupporting

confidence: 68%

In vitroassembly of the Rous Sarcoma Virus capsid protein into hexamer tubes under physiological conditions

Jaballah

Bailey

Desfosses

et al. 2017

Preprint

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“…Systems with different binding mode and binding geometry can be explored in details. An example is the HIV-1 viral capsid nucleation process [5]. In addition, critical steps of the blood-clotting processes involving fibrin and other molecules in the blood-clotting process [17] can also be studied.…”

Section: Discussionmentioning

confidence: 99%

“…Following [5], we analyzed the elasticity and sensitivity of parameters of the CF system for a subset of clusters present at different ratio of a i,j /d i,j . Here, we use sensitivity to examine the response of the expected number of different clusters to changes in a i,j /d i,j .…”

Section: Dynamical Behavior Of the Cf Systemmentioning

confidence: 99%

“…We Table 3: The convergence behavior of the system at different time steps at different ratios of the attachment to detachment rates use elasticity to examine the relative changes in the expected number of different clusters with respect to the relative changes in a i,j /d i,j . Following [5], the sensitivity Se and the elasticity El of forming a cluster of size i are calculated as Fig. 7 shows Se and El for formation of 4 clusters of sizes 4, 8, 12, and 16 at 3 different a i,j /d i,j of 5, 20, and 50.…”

Section: Dynamical Behavior Of the Cf Systemmentioning

confidence: 99%

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Evolution of coagulation-fragmentation stochastic processes using accurate chemical master equation approach

Manuchehrfar

Tian

Chou

et al. 2019

Communications in Information and Systems

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Coagulation and fragmentation (CF) is a fundamental process by which particles attach to each other to form clusters while existing clusters break up into smaller ones. It is a ubiquitous process that plays a key role in many physical and biological phenomena. CF is typically a stochastic process that often occurs in confined spaces with a limited number of available particles. In this study, we use the discrete Chemical Master Equation (dCME) to describe the CF process. Using the newly developed Accurate Chemical Master Equation (ACME) method, we calculate the time-dependent behavior of the CF system. We investigate the effects of a number important factors that influence the overall behavior of the system, including the dimensionality, the ratio of attachment to detachment rates among clusters, and the initial conditions. By comparing CF in one and three dimensions we conclude that systems in higher dimensions are more likely to form large clusters. We also demonstrate how the ratio of the attachment to detachment rates affect the dynamics and the steady-state of the system. Finally, we demonstrate the relationship between the formation of large clusters and the initial condition.

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“…These researchers analyzed the relationship between the timing of the initial appearance of HIV-1 capsid on the PM and the various model parameters. Sadre-Marandi et al [ 8 ] and Liu et al [ 9 ] simulated HIV-1 viral capsid assembly through dynamical systems.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling and quantitative analysis of HIV-1 Gag trafficking and polymerization

Liu¹,

Zou²

2017

PLoS Comput Biol

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Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed. Using our model, we analyzed the weight of the pathways involved in the polymerization reactions and concluded that the predominant pathways for the formation of a hexamer might be the polymerization of two monomers to form a dimer, the polymerization of a dimer and a monomer to form a trimer, and the polymerization of two trimers to form a hexamer. We then deduced that the dimer and trimer intermediates might be crucial in hexamer formation. We also explored four theoretical combined methods for Gag suppression, and hypothesized that the N-terminal glycine residue of the MA domain of Gag might be a promising drug target. This work serves as a guide for future theoretical and experimental efforts aiming to understand HIV-1 Gag trafficking and polymerization, and might help accelerate the efficiency of anti-AIDS drug design.

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Modeling HIV-1 viral capsid nucleation by dynamical systems

Cited by 7 publications

References 41 publications

In vitroassembly of the Rous Sarcoma Virus capsid protein into hexamer tubes under physiological conditions

In vitroassembly of the Rous Sarcoma Virus capsid protein into hexamer tubes under physiological conditions

Evolution of coagulation-fragmentation stochastic processes using accurate chemical master equation approach

Mathematical modeling and quantitative analysis of HIV-1 Gag trafficking and polymerization

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