Limits...
An assembly funnel makes biomolecular complex assembly efficient.

Zenk J, Schulman R - PLoS ONE (2014)

Bottom Line: For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific.However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions.The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis.

View Article: PubMed Central - PubMed

Affiliation: Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.

ABSTRACT
Like protein folding and crystallization, the self-assembly of complexes is a fundamental form of biomolecular organization. While the number of methods for creating synthetic complexes is growing rapidly, most require empirical tuning of assembly conditions and/or produce low yields. We use coarse-grained simulations of the assembly kinetics of complexes to identify generic limitations on yields that arise because of the many simultaneous interactions allowed between the components and intermediates of a complex. Efficient assembly occurs when nucleation is fast and growth pathways are few, i.e. when there is an assembly "funnel". For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific. However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions. The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis.

Show MeSH

Related in: MedlinePlus

Self-assembly model for a 4-component square grid (“2×2”) complex.The square, rigid components have specific binding rules on each edge denoted by edge colors. Like colored edges interact, whereas edges with different colors and black edges do not interact. An initial, fixed number of components is depleted during self-assembly. At the end of the process, the solution contains a mixture of components, intermediates and complexes.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4215988&req=5

pone-0111233-g001: Self-assembly model for a 4-component square grid (“2×2”) complex.The square, rigid components have specific binding rules on each edge denoted by edge colors. Like colored edges interact, whereas edges with different colors and black edges do not interact. An initial, fixed number of components is depleted during self-assembly. At the end of the process, the solution contains a mixture of components, intermediates and complexes.

Mentions: To characterize the kinetics of complex assembly, we use a simple model of assembly in which rigid components of a generic complex bind to one another via orientation-specific pairs of complementary interfaces (Fig. 1). We assume that all components have identical interaction energy at each interface and the same initial concentration. Interaction between non-matching interfaces, or crosstalk, is neglected, reflecting rapid advances in the design of specific biomolecular interfaces [14], [24]–[26], [33], [34]. Multiple different rigid components and their unique interfaces could be easily fabricated from DNA, for example, using existing techniques such as DNA origami [27] or DNA bricks [25]. In our model, we consider all binary reactions that produce a complex or any connected subset of components, which we call intermediates (see Supporting Methods).


An assembly funnel makes biomolecular complex assembly efficient.

Zenk J, Schulman R - PLoS ONE (2014)

Self-assembly model for a 4-component square grid (“2×2”) complex.The square, rigid components have specific binding rules on each edge denoted by edge colors. Like colored edges interact, whereas edges with different colors and black edges do not interact. An initial, fixed number of components is depleted during self-assembly. At the end of the process, the solution contains a mixture of components, intermediates and complexes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215988&req=5

pone-0111233-g001: Self-assembly model for a 4-component square grid (“2×2”) complex.The square, rigid components have specific binding rules on each edge denoted by edge colors. Like colored edges interact, whereas edges with different colors and black edges do not interact. An initial, fixed number of components is depleted during self-assembly. At the end of the process, the solution contains a mixture of components, intermediates and complexes.
Mentions: To characterize the kinetics of complex assembly, we use a simple model of assembly in which rigid components of a generic complex bind to one another via orientation-specific pairs of complementary interfaces (Fig. 1). We assume that all components have identical interaction energy at each interface and the same initial concentration. Interaction between non-matching interfaces, or crosstalk, is neglected, reflecting rapid advances in the design of specific biomolecular interfaces [14], [24]–[26], [33], [34]. Multiple different rigid components and their unique interfaces could be easily fabricated from DNA, for example, using existing techniques such as DNA origami [27] or DNA bricks [25]. In our model, we consider all binary reactions that produce a complex or any connected subset of components, which we call intermediates (see Supporting Methods).

Bottom Line: For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific.However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions.The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis.

View Article: PubMed Central - PubMed

Affiliation: Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.

ABSTRACT
Like protein folding and crystallization, the self-assembly of complexes is a fundamental form of biomolecular organization. While the number of methods for creating synthetic complexes is growing rapidly, most require empirical tuning of assembly conditions and/or produce low yields. We use coarse-grained simulations of the assembly kinetics of complexes to identify generic limitations on yields that arise because of the many simultaneous interactions allowed between the components and intermediates of a complex. Efficient assembly occurs when nucleation is fast and growth pathways are few, i.e. when there is an assembly "funnel". For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific. However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions. The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis.

Show MeSH
Related in: MedlinePlus