Author Archives: Daniel Nissley

An in vivo force sensor reveals varied mechanisms of co-translational force generation

This blog post comments on the results published by Fujiwara and co-workers in the 2020 Cell Reports article “Proteome-wide capture of co-translational protein dynamics in Bacillus subtilis using TnDR, a transposable protein-dynamics reporter.”

The study of mechanical force generation and its influence on biological systems has expanded in recent years. In the realm of nascent protein folding, we now know that both unstructured and folded nascent proteins generate forces on the order of piconewtons that propagate down the nascent chain. These forces can distort the functional site of the ribosome and may influence the rate of translation (PMIDs: 30824598, 29577725). It has also been shown that translational arrest can be relieved by mechanical force (PMID: 25908824). Much study has focused on so-called arrest peptides, short peptide sequences that interact so strongly with the ribosome exit tunnel that they can completely stall translation (e.g., SecM, MifM).

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Electrostatic interactions govern extreme nascent protein ejection times from ribosomes and can delay ribosome recycling

Finishing up a lingering project from your PhD almost a year into your postdoc is a great feeling, especially when it has actually been about 3 years in the making.

Though somewhat outside of the usual scope of activities in OPIG, I encourage you to take a look if the below summary grabs your interest. The full paper and supporting materials (including some movies which took entirely too long to make) can be found at https://pubs.acs.org/doi/abs/10.1021/jacs.9b12264.

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Molecular dynamics analysis in MDAnalysis

Any opportunity to use rigorously tested and supported analysis tools rather than in-house code is, in my opinion, an opportunity you owe it to yourself to explore.

My preferred tool for analyzing the output of molecular dynamics (MD) simulations is MDAnalysis, a Python library that provides robust and easy-to-use tools for analyzing most common files output by MD packages (including PDB, DCD, COR, and XTC file formats). But, of course, MDAnalysis can analyze any PDB file, not just one output from an MD simulations. There may be an opportunity in your workflow to incorporate MDAnalysis to save time or to provide more robust error handling than whatever in-house code you currently use.

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The address of a gene

Most scientists working in the biological sciences or an overlapping field have encountered various ways of identifying genes and proteins. There are many different types of identifiers. For example, searching for the PDB ID: 2IW3 (which represents elongation factor 3 in yeast strain S288C) on UniProt gives us a results column labeled “Gene names” that includes no less than six (!) ways to refer to the gene that produces this particular protein. This can be frustrating – it is easy to get into trouble when you think you have a consistent gene naming scheme when you do not, especially if you want to cross-reference gene lists.

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OpenMM – easy to learn, highly flexible molecular dynamics in Python

When I came to OPIG this past March I realized I had a novel opportunity – there was no one to tell me which molecular dynamics (MD) program I had to use! Usually, researchers do not have much choice in the matter due to a number of practical concerns. Conflicts between input and output file formats, forces, velocities, and basically everything else between MD suites make having multiple programs flying around tenuous at best if you want group members to be able to help one another. After weighing my options, I settled on OpenMM – and so far I am very happy with the decision.

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