scholarly journals Viral genome structures are optimal for capsid assembly

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Jason D Perlmutter ◽  
Cong Qiao ◽  
Michael F Hagan
Keyword(s):  
Negative Charge ◽  
Tertiary Structure ◽  
Theoretical Models ◽  
Coarse Grained ◽  
Capsid Assembly ◽  
Optimal Length ◽  
Viral Propagation ◽  
Coarse Grained Model ◽  
Virus Capsids ◽  
Thermodynamic Basis

Understanding how virus capsids assemble around their nucleic acid (NA) genomes could promote efforts to block viral propagation or to reengineer capsids for gene therapy applications. We develop a coarse-grained model of capsid proteins and NAs with which we investigate assembly dynamics and thermodynamics. In contrast to recent theoretical models, we find that capsids spontaneously ‘overcharge’; that is, the negative charge of the NA exceeds the positive charge on capsid. When applied to specific viruses, the optimal NA lengths closely correspond to the natural genome lengths. Calculations based on linear polyelectrolytes rather than base-paired NAs underpredict the optimal length, demonstrating the importance of NA structure to capsid assembly. These results suggest that electrostatics, excluded volume, and NA tertiary structure are sufficient to predict assembly thermodynamics and that the ability of viruses to selectively encapsidate their genomic NAs can be explained, at least in part, on a thermodynamic basis.

scholarly journals The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Zareh A. Grigoryan ◽  
Armen T. Karapetian
Keyword(s):  
Phase Transition ◽  
Secondary Structure ◽  
Characteristic Time ◽  
Tertiary Structure ◽  
Mutual Influence ◽  
Coarse Grained ◽  
Nonequilibrium Phase Transition ◽  
Nonequilibrium Phase ◽  
Coarse Grained Model ◽  
Structure Rearrangement

The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA) in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed.

scholarly journals Generic, phenomenological, on-the-fly renormalized repulsion model for self-limited organization of terminal supraparticle assemblies

2015 ◽  
Vol 112 (25) ◽  
pp. E3161-E3168 ◽  
Author(s):  
Trung Dac Nguyen ◽  
Benjamin A. Schultz ◽  
Nicholas A. Kotov ◽  
Sharon C. Glotzer
Keyword(s):  
Soft Matter ◽  
Dimensionless Parameter ◽  
Shell Morphology ◽  
Coarse Grained ◽  
Promising Candidate ◽  
Coarse Grained Model ◽  
Colloidal Aggregates ◽  
Virus Capsids ◽  
Dynamics Simulations ◽  
Potential Use

Self-limited, or terminal, supraparticles have long received great interest because of their abundance in biological systems (DNA bundles and virus capsids) and their potential use in a host of applications ranging from photonics and catalysis to encapsulation for drug delivery. Moreover, soft, uniform colloidal aggregates are a promising candidate for quasicrystal and other hierarchical assemblies. In this work, we present a generic coarse-grained model that captures the formation of self-limited assemblies observed in various soft-matter systems including nanoparticles, colloids, and polyelectrolytes. Using molecular dynamics simulations, we demonstrate that the assembly process is self-limited when the repulsion between the particles is renormalized to balance their attraction during aggregation. The uniform finite-sized aggregates are further shown to be thermodynamically stable and tunable with a single dimensionless parameter. We find large aggregates self-organize internally into a core–shell morphology and exhibit anomalous uniformity when the constituent nanoparticles have a polydisperse size distribution.

scholarly journals Analyzing the electrogenicity of cytochrome c oxidase

2016 ◽  
Vol 113 (28) ◽  
pp. 7810-7815 ◽  
Author(s):  
Ilsoo Kim ◽  
Arieh Warshel
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Theoretical Models ◽  
Proton Pumping ◽  
Coarse Grained ◽  
Transfer Reactions ◽  
Coarse Grained Model ◽  
Fundamental Information ◽  
Wide Range ◽  
Charge Transfer Reactions

Measurements of voltage changes in response to charge separation within membrane proteins can offer fundamental information on spectroscopically “invisible” steps. For example, results from studies of voltage changes associated with electron and proton transfer in cytochrome c oxidase could, in principle, be used to discriminate between different theoretical models describing the molecular mechanism of proton pumping. Earlier analyses of data from these measurements have been based on macroscopic considerations that may not allow for exploring the actual molecular mechanisms. Here, we have used a coarse-grained model describing the relation between observed voltage changes and specific charge-transfer reactions, which includes an explicit description of the membrane, the electrolytes, and the electrodes. The results from these calculations offer mechanistic insights at the molecular level. Our main conclusion is that previously assumed mechanistic evidence that was based on electrogenic measurements is not unique. However, the ability of our calculations to obtain reliable voltage changes means that we have a tool that can be used to describe a wide range of electrogenic charge transfers in channels and transporters, by combining voltage measurements with other experiments and simulations to analyze new mechanistic proposals.

Insights Into Crowding Effects on Protein Stability From a Coarse-Grained Model

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Vincent K. Shen ◽  
Jason K. Cheung ◽  
Jeffrey R. Errington ◽  
Thomas M. Truskett
Keyword(s):  
Protein Stability ◽  
Coarse Grained ◽  
Protein Solutions ◽  
Native State ◽  
High Concentration ◽  
Coarse Grained Model ◽  
Excluded Volume Effects ◽  
Thermodynamic Phase ◽  
Broad Interest ◽  
Liquid Liquid Phase Separation

Proteins aggregate and precipitate from high concentration solutions in a wide variety of problems of natural and technological interest. Consequently, there is a broad interest in developing new ways to model the thermodynamic and kinetic aspects of protein stability in these crowded cellular or solution environments. We use a coarse-grained modeling approach to study the effects of different crowding agents on the conformational equilibria of proteins and the thermodynamic phase behavior of their solutions. At low to moderate protein concentrations, we find that crowding species can either stabilize or destabilize the native state, depending on the strength of their attractive interaction with the proteins. At high protein concentrations, crowders tend to stabilize the native state due to excluded volume effects, irrespective of the strength of the crowder-protein attraction. Crowding agents reduce the tendency of protein solutions to undergo a liquid-liquid phase separation driven by strong protein-protein attractions. The aforementioned equilibrium trends represent, to our knowledge, the first simulation predictions for how the properties of crowding species impact the global thermodynamic stability of proteins and their solutions.

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