Christian Blau

Dynamic contact network between ribosomal subunits enables rapid large-scale rotation during spontaneous translocation

During ribosomal translation, the two ribosomal subunits remain associated through intersubunit bridges, despite rapid large-scale intersubunit rotation. The absence of large barriers hindering rotation is a prerequisite for rapid rotation. Here, we investigate how such a flat free-energy landscape is achieved, in particular considering the large shifts the bridges undergo at the periphery. The dynamics and energetics of the intersubunit contact network are studied using molecular dynamics simulations of the prokaryotic ribosome in intermediate states of spontaneous translocation. Based on observed occupancies of intersubunit contacts, residues were grouped into clusters. In addition to the central contact clusters, peripheral clusters were found to maintain strong steady interactions by changing contacts in the course of rotation. The peripheral B1 bridges are stabilized by a changing contact pattern of charged residues that adapts to the rotational state. In contrast, steady strong interactions of the B4 bridge are ensured by the flexible helix H34 following the movement of protein S15. The tRNAs which span the subunits contribute to the intersubunit binding enthalpy to an almost constant degree, despite their different positions in the ribosome. These mechanisms keep the intersubunit interaction strong and steady during rotation, thereby preventing dissociation and enabling rapid rotation.

g_contacts: Fast contact search in bio-molecular ensemble data ✩,✩✩

a b s t r a c t Short-range interatomic interactions govern many bio-molecular processes. Therefore, identifying close interaction partners in ensemble data is an essential task in structural biology and computational biophysics. A contact search can be cast as a typical range search problem for which efficient algorithms have been developed. However, none of those has yet been adapted to the context of macromolecular ensembles, particularly in a molecular dynamics (MD) framework. Here a set-decomposition algorithm is implemented which detects all contacting atoms or residues in maximum O(N log(N)) run-time, in contrast to the O(N 2 ) complexity of a brute-force approach.

Inference of Calmodulin’s Ca2+-Dependent Free Energy Landscapes via Gaussian Mixture Model Validation

A free energy landscape estimation method based on the well-known Gaussian mixture model (GMM) is used to compare the efficiencies of thermally enhanced sampling methods with respect to regular molecular dynamics. The simulations are carried out on two binding states of calmodulin, and the free energy estimation method is compared with other estimators using a toy model. We show that GMM with cross-validation provides a robust estimate that is not subject to overfitting. The continuous nature of Gaussians provides better estimates on sparse data than canonical histogramming. We find that diffusion properties determine the sampling method effectiveness, such that diffusion-dominated apo calmodulin is most efficiently sampled by regular molecular dynamics, while holo calmodulin, with its rugged free energy landscape, is better sampled by enhanced sampling methods.

Inference of Calmodulin's Ca2+ : Dependent Free Energy Landscapes via Gaussian Mixture Model Validation

Inference of Calmodulins Ca2+ : Dependent Free Energy Landscapes via Gaussian Mixture Model Validation

In Silico Examination Of The Influence Of Nucleotide Modifications And Magnesium Ions On tRNA Structure And Dynamics

In our work the influence of chemical modificatons and ions on RNA structure and dynamics has been tested. The effect of nucleotide modifications on E. coli and yeast tRNA in solution has been examined with a molecular dynamics approach. Simulations show a decrease of helical content in RNA secondary structure due to those modifications. In another step magnesium ion binding effects on the same tRNA were looked at by performing simulations with and without ions bound to tRNA. Ions coordinating nucleotides in those simulations show them highly affecting local secondary structure motifs. Thus the simulations performed give new hints on the function of nulceotide modifications and ion binding to RNA.