Macromolecular Modeling Blog ™

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.

Dates: 2-3 September, 2010

Venue: ETH Zürich, Lecture Hall HG E7, Zürich, Switzerland

Confirmed plenary lecturer: James U. Bowie, Kathryn M. Ferguson, John Kuriyan, Jonathon Howard, Jan Löwe, Krzystof Palcezski, Bob Stround.

This symposium series provides a yearly update on current structural biology themes and newest developments in the field. Renowned structural biology scientists from all over the world exchange their knowledge and current research ideas in an interactive way. The format of the symposium includes plenary lectures by invited guest scientists, discussions and poster presentations by NCCR scientists.

More details on the meeting website

PyRosetta Book

The Gray Lab at Johns Hopkins University has just released PyRosetta, a Python-based interactive platform for accessing the objects and algorithms within the Rosetta protein structure prediction suite.

In addition to the code, the Gray Lab has put together a book that leads the reader through basics of protein structure and energetics to applications in folding, refinement, docking and design. The focus is on enabling users to write custom scripts, so it includes material on Rosetta fundamentals and the appendices have a list of PyRosetta commands and a breakdown of the input files. The book was beta-tested by students during a course at JHU. The course is a series of workshops that teach how to measure and manipulate protein conformations, calculate energies in low- and high-resolution representations, fold proteins from sequence, model variable regions of proteins (loops), dock proteins or small molecules, design protein sequences, and build custom protocols for operations tailored to particular biomolecular applications

The book can be purchased through Lulu:

http://www.lulu.com/content/paperback-book/the-pyrosetta-interactive-platform-for-protein-structure-prediciton-and-design-a-set-of-educational-modules/7187010

or downloaded for free as pdf chapters from http://www.pyrosetta.org under the Tutorial link.

We recently saw these posts reporting that Warren DeLano passed away on Tuesday:

https://www.jiscmail.ac.uk/cgi-bin/webadmin?A2=CCP4BB;19EK9w;20091105105413-0800

http://www.macresearch.org/memoriam-warren-l-delano

This is a terrible tragedy and our hearts go out to his family and friends. He was a truly incredible person whose work with PyMOL changed the face of molecular modeling. He also had a huge personal impact on our community. He was dedicated to science and dedicated to making the world a better place through his example and by the personal way he interacted with everyone.

When I was considering starting the Rosetta Design Group a few years back, I asked Warren for some advice by email. He promptly called and we talked for a few hours. After our conversation I reflected on how much his call and advice meant to me, and hoped that I would act as he did in the same situation.

May his example, memory, and code live on forever.

My jaw dropped when I saw this. Hilarious. Scary. So true.

Molecular Modelers have Aspergers

Its from: http://en.wikipedia.org/wiki/Asperger_syndrome

A variety of groups have sprung up on LinkedIn that may be of interest to macromolecular modelers. In these groups, there are job postings, literature reviews and notices, discussions, and more. Below is a list of groups that we have joined. Do you know of a group that is not listed below?

Antibody Network

Biotech & Pharma Professionals Network

Computational Biology

Protein engineering

Structure-Based Drug Design

Molecular Modeling in Life Sciences

In a post yesterday on the Bleeding Edge Biotech Blog, Adam Kraut gives an expanded version of his article for Bio-IT World entitled Antibody Docking on the Amazon Cloud describing how Pfizer is leveraging the power and flexibility of cloud computing to run antibody docking simulations using Rosetta. Pfizer employed BioTeam (which Kraut consults for) to port Rosetta to the cloud. This is a fascinating article and certainly the Pfizer/BioTeam/Rosetta/Amazon synergy is a phenomenon on the bleeding edge.

I would add to the article that Jeffrey Gray at Johns Hopkins University was the lead developer of RosettaDock and RosettaAntibody. Rosetta has become synonymous with David Baker (and for good reason), but it is important to acknowledge continuing contributions to Rosetta outside of the Baker lab. Scientific collaborations can dissolve quickly when recognition is unevenly distributed, whether internally or as a result of outside perceptions (i.e. not as the result of any intentions by researchers in the collaboration).

If you use or write about Rosetta, please help us keep this unique collaboration going by acknowledging and citing the individual developers and researchers and their current labs!!!!