Macromolecular Modeling Blog ™

A collection of interesting papers from the recent literature – there’s something for everyone here. Enjoy.

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About a year ago we reported of PLoS and Molsoft launching a new way of publishing structural biology related papers. A couple of days ago I’ve stumbled on one such paper, published in PLoS biology and decided to take the technology for a ride.

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Cryo-EM single particle analysis is a method for determining structures of large molecules and macromolecular assemblies at resolutions ranging from 3.5- 30 A. Interpreting the density maps produced by this technique represents an ongoing challenge, for which molecular modeling techniques offer some unique solutions.

Over the last five years, cryo-EM single particle analysis has begun producing structures at resolutions better than 5 A, with subnanometer resolutions becoming common. At resolutions between 5 and 9 A it becomes possible to move beyond simple rigid-body docking and alter atomistic models to reposition helices and sheets, to better fit the cryo-EM based density maps. At 3-5 A resolution de-novo C-alpha traces and in some cases full atomistic models can be constructed directly from the cyro-EM density without invoking x-ray crystallography.

We call this a challenge rather than a contest because, unlike CASP, there is no hidden answer to be revealed. In this project, we provide publicly available cryo-EM densities for a selected set of structures at different resolutions, and challenge those in the modeling community to apply their tools to extract as much information as they can from each. At the end, the results will be evaluated by comparing the results of different groups, and validating against any other existing knowledge about each target. We hope this will yield new insights into these published structures, and at the very least, it will establish the capabilities of current modeling methods, and give the cryo-EM community some guidance as to how to proceed with maps in various resolution ranges. For modelers it provides a new area in which to apply/develop their techniques, and demonstrating your tools’ capabilities may lead to new opportunities for collaboration.

Please see the challenge website for more details.

We launched a new Jobs page.

If you’re looking to hire – fill in the form at the top of the page. If you’re looking for a molecular modeling job – search the jobs (posted in reverse chronological date)

Molecular Modeling Jobs

We hope this resource would help both employers and modelers.

A postdoctoral researcher is sought to conduct fundamental computational research to understand molecular origins of aggregation in protein therapeutics, especially monoclonal antibodies and antibody based therapeutics. The research shall involve an inter-disciplinary mix of statistical analyses, bioinformatics, high performance grid computing, molecular biophysics, molecular modeling, and simulation techniques to advance our understanding of protein structure-function-aggregation relationships and mechanism(s) of aggregation. The researcher shall be expected to develop novel approaches to detect aggregation prone regions and three dimensional aggregation prone motifs and suggest ways to improve manufacturability of biotherapeutics via rational design.

For detailed job focus, responsibilities and qualifications, please access http://www.pfizer.com/careers and use code 941315.

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Are you tired of manually editing PDB files ?

Checkout this PDB mode for Emacs that helps you do most of the usual modeler editing tasks in a press of a button.

Via @leninwtigger

JOB DESCRIPTION

We are searching for a highly motivated scientist with expertise in macromolecular structure analysis, modeling, and prediction, molecular docking, and/or molecular dynamics simulations to support the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH).

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There is a new website for job openings in Rosetta Commons labs:

http://www.rosettacommons.org/positions/index.html

I highly recommend working with any of the PI’s in the Rosetta Commons labs. They’re great folks and great scientists (and most of the labs happen to be in great locations too!).

In a recent post, Derek Lowe, from “In The Pipeline”, asks his readership “If we could just walk right up and calculate the free energies of binding events reliably, what would you most want such calculations to be able to do for you? What would convince you that they’re actually believable? And how close to you think that we actually are to that?” We tried to briefly answer some of these questions. How close are we to predict small molecules binding free energy?

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How do enzymes catalyze reactions? There are countless answers of course, but one answer that has gained much attention and popularity in recent years is – through intrinsic dynamics. Is that so? PNAS recently published a paper by Arieh Warshel entitled: “Enzyme millisecond conformational dynamics do not catalyze the chemical step”. Warshel, an avid assailant of the coupling between dynamics and catalysis was met by Martin Karplus, devoted advocate for catalytic dynamics, to engage in a public dispute over the letters section of PNAS. Who do you find more convincing?

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