How Does a 30S Ribosome Find Its Target on an mRNA?

To initiate translation in prokaryotes, the 30S ribosome must bind to the Ribosomal Binding Site (RBS) on the mRNA. The rate at which this process occurs affects the overall efficiency of the translation process and thus impacts the speed at which prokaryotes can grow and divide. Experimental evidence that 80% of ribosomes are actively translating suggests the search process may represent a significant biophysical challenge for the cell, and further places a rough upper limit of 4s on the time the search process may take. This bound is significantly exceeded by a search that only utilizes the free 3D diffusion of the 30S and mRNA, suggesting that the 30S may perform local searches on each mRNA to which it nonspecifically binds. Here, we employ a simple theoretical framework to examine several possibilities for these local searches. The 30S may: 1) diff use along the mRNA in 1D; 2) simultaneously bind to two sites along the mRNA chain and perform an Intersegmental Transfer (IT) between them; 3) diffuse within the mRNA coil; or 4) utilize a combination of these strategies. We demonstrate that nearly all these search strategies may be fast enough to be biologically viable; however, in comparing our results to recent in vitro experiments measuring the dissociation rate of the 30S from the mRNA (Mil on et al., 2012), we find that the most likely candidates for the search process are searches using ITs that do not include diffusion within the mRNA coil. Finally, we suggest future in vitro experiments, based on the predicted scaling behavior of the search time and dissociation rate with mRNA length and concentration, whose results may indicate which search strategy is used by the 30S

Uncovering the mechanism for aggregation in repeat expanded RNA reveals a reentrant transition

RNA molecules aggregate in certain conditions, but how and why remains unclear. Here the authors develop a model that quantitatively explains the conditions and mechanism of RNA aggregation, and predicts a surprising non-monotonicity in the transition

A computational toolbox for the assembly yield of complex and heterogeneous structures

The self-assembly of complex structures from a set of non-identical building blocks is a hallmark of soft matter and biological systems, including protein complexes, colloidal clusters, and DNA-based assemblies. Predicting the dependence of the equilibrium assembly yield on the concentrations and interaction energies of building blocks is highly challenging, owing to the difficulty of computing the entropic contributions to the free energy of the many structures that compete with the ground state configuration. While these calculations yield well known results for spherically symmetric building blocks, they do not hold when the building blocks have internal rotational degrees of freedom. Here we present an approach for solving this problem that works with arbitrary building blocks, including proteins with known structure and complex colloidal building blocks. Our algorithm combines classical statistical mechanics with recently developed computational tools for automatic differentiation. Automatic differentiation allows efficient evaluation of equilibrium averages over configurations that would otherwise be intractable. We demonstrate the validity of our framework by comparison to molecular dynamics simulations of simple examples, and apply it to calculate the yield curves for known protein complexes and for the assembly of colloidal shells