NAMD Developer Workshop on May 26-27 in Chicago, IL

We are pleased to invite you to the first edition of the NAMD developer workshop jointly organized by the University of Illinois, Urbana-Champaign and the University of Chicago, and to be held on the campus of the University of Chicago.

This workshop is intended to gather the community of NAMD developers for fruitful exchange on current and future developments of the program. It will consist of short presentations aimed at covering practical coding aspects, ongoing developments, architecture specificities, implementations of novel algorithms, as well as broader topics, notably future directions of the program and the parallel programming environment charm++ it uses.

This workshop is not intended for scientific presentations about applications, although illustrative applications of on-going code developments would be welcome.

The workshop will be held at the Gordon Center for Integrative Science on the University of Chicago campus and is sponsored by:

National Institute of General Medical Sciences
NIH Center for Macromolecular Modeling and Bioinformatics (NIH 9P41GM104601)
NIH Hands-on Workshops on Computational Biophysics (NIH 1R25GM103771-01)
The Membrane Protein Structural Dynamics Consortium (NIH grant NIGMS U54-GM087519)

For more information and registration, visit this page.

Active MPSDC participation in the Biophysical Society 60th Annual Meeting in 2016

MPSDC Awards: Francisco Bezanilla, Past President presenting an award to Robert Nakamoto.
(Click to enlarge)

The Membrane Protein Structural Dynamics Consortium is always very well represented at the annual Biophysical Society meeting, as can be seen by Klaus Schulten‘s National Lecture in 2015 as well as at the level of participants in a remarkably large number of workshops, symposia, and presentations. This is also reflected in Consortium members being actively involved at the leadership level, including Francisco Bezanilla‘s tenure as Biophysical Society President from 2012 to 2014 and Robert Nakamoto and Olga Boudker‘s service in the current Biophysical Society leadership council.

On August 31, 2015 the Biophysical Society announced that MPSDC Chair Eduardo Perozo was elected as a 2016 Society Fellow. This award honors the Society’s distinguished members who have demonstrated excellence in science, contributed to the expansion of the field of biophysics, and supported the Biophysical Society. The Fellows will be honored at the Awards Ceremony during the Biophysical Society’s 60th Annual Meeting on Monday February 29, 2016 at the Los Angeles Convention Center in Los Angeles, California. Perozo was elected for his leadership and fundamental contributions in ion channel biophysics.

At next year’s meeting in Los Angeles, MPSDC members will participate in a number of specialty symposia and workshops organized by the Biophysical society (more information on the nature of these symposia and workshops can be found on the Biophysical Society meeting website here). We would like to highlight the following in particular (though there are and will certainly be more ways in which Consortium members are involved with the meeting):

  • Francisco Bezanilla (University of Chicago) is participating in a symposium on Voltage Sensing and Gating.
  • Olga Boudker (Weill Cornell Medical College) is receiving the Michael and Kate Bárány Award during the meeting’s award symposium. During this session, award recipients are recognized and each give a short talk about the work for which they are being recognized. Congratulations, Olga!
  • Yifan Cheng (University of California, San Francisco) is co-chairing the Cryo-EM Subgroup 2016 Symposium
  • Claudio Grosman(UIUC) is participating in a symposium on Pentameric Ligand-gated Ion Channels: New Insights from Structure and Function.
  • Benoît Roux (University of Chicago) is participating in a workshop about Computational Methods for Ion Permeation and Selectivity
  • Emad Tajkhorshid (UIUC) will once again be chairing the Permeation & Transport Subgroup 2015 Symposium. He chaired the same subgroup last year.

Last year, MPSDC member and one of our keynote speakers at Frontiers in Membrane Protein Structural Dynamics 2014 Klaus Schulten (UIUC) gave the prestigious National Lecture. The National Lecturer is the highest award given each year by the Biophysical Society. Dr. Schulten’s 2015 National Lecture lecture can be viewed in full here.

See also: interviews from the 59th Biophysical Society Meeting with 2015 National Lecturer Klaus Schulten and Harel Weinstein.

See also: interviews from the 58th Biophysical Society Meeting with Francisco Bezanilla, Past President and Robert Nakamoto, Chair of the 2014 BPS Program Committee.

MPSDC Chair Eduardo Perozo to speak at Frontiers in Integral Membrane Protein Structural Biology in Oxford

Structural biology of membrane proteins, particularly from higher eukaryotes, has been transformed in the last two years. New and improved technologies such as electron microscopy and free electron lasers have led to the rapid increase in the number of structures solved and the complexity of these structures. This symposium will highlight advances in technology, celebrate the unprecedented advances in understanding of membrane protein structure and function, and look to the future for this rapidly developing field.

Frontiers in Integral Membrane Protein Structural Biology 2015 is set to take place in Oxford, United Kingdom from October 5th until the 7th.

MPSDC Chair Eduardo Perozo will participate with a lecture titled “Asymmetric Conformational Transition Underlies Mg2+-Driven Gating in CorA.”

Former MPSDC-sponsored Frontiers in Membrane Protein Structural Dynamics conference speakers Robert Stroud (who gave of the two 2014 keynote lectures) and Robert Tampé are also participating.

Learn more about the symposium »

Solving a Major Piece of a Cellular Mystery about Nuclear Pore Complexes

Drs. Shohei Koide and Anthony Kossiakoff recently worked together with a team to determines the architecture of a second subcomplex of the nuclear pore complex, in so doing solving a major quandary of answering how a nuclear pore complex (NPC) can be such an effective gatekeeper, preventing much from entering the nucleus while helping to shuttle certain molecules across the nuclear envelope.

The scientific team was featured in multiple publications including Caltech and the Argonne National Laboratory Science Highlights (reproduced in part below). The research was supported in part by the Consortium, and culminated in the following publication:

Architecture of the fungal nuclear pore inner ring complex

Stuwe T, Bley CJ, Thierbach K, Petrovic S, Schilbach S, Mayo DJ, Perriches T, Rundlet EJ, Jeon YE, Collins LN, Huber FM, Lin DH, Paduch M, Koide A, Lu V, Fischer J, Hurt E, Koide S, Kossiakoff AA, Hoelz A. Science. 2015 Oct 2;350(6256):56-64. PMID: 26316600.

Learn more »

Solving a Major Piece of a Cellular Mystery

This article by Argonne reproduced in part can be read here

Not just anything is allowed to enter the nucleus, the heart of eukaryotic cells where, among other things, genetic information is stored. A double membrane, called the “nuclear envelope,” serves as a wall, protecting the contents of the nucleus. Any molecules trying to enter or exit the nucleus must do so via a cellular gatekeeper known as the nuclear pore complex (NPC), or pore, which exists within the envelope.

How can the NPC be such an effective gatekeeper — preventing much from entering the nucleus while helping to shuttle certain molecules across the nuclear envelope? Scientists have been trying to figure that out for decades, at least in part because the NPC is targeted by a number of diseases, including some aggressive forms of leukemia and nervous system disorders such as a hereditary form of Lou Gehrig’s disease. Now a team of researchers from Caltech, The University of Chicago, and the Biochemistry Center of Heidelberg University (Germany), led by André Hoelz and working at three U.S. Department of Energy synchrotron light sources including the Advanced Photon Source (APS) at Argonne, has solved a crucial piece of the puzzle.

In February of this 2015, the team published a paper describing the atomic structure of the NPC’s coat nucleoporin complex, a subcomplex that forms what they now call the outer rings (see the figure). Building on that work, the team has now solved the architecture of the pore’s inner ring, a subcomplex that is central to the NPC’s ability to serve as a barrier and transport facilitator. In order to determine that architecture, which determines how the ring’s proteins interact with each other, the biochemists built up the complex in a test tube and then systematically dissected it to understand the individual interactions between components. Then they validated that this is actually how it works in vivo, in a species of fungus.

Read more »

Researchers discover structure of fluoride-specific ion channel

Dr. Shohei Koide‘s collaborations in a scientific team seeking to discover the structure of a fluoride-specific ion channel was recently featured in Brandeis NOW, a scientific research publication published by Brandeis University. The work focuses on Dr. Christopher Miller’s lab, based at Brandeis University. The research was supported in part by the Consortium, and culminated in the following publication:

Crystal structures of a double-barrelled fluoride ion channel

Stockbridge RB, Kolmakova-Partensky L, Shane T, Koide A, Koide S, Miller C, Newstead S. Nature. 2015 Sep 24;525(7570):548-51. PMID: 26344196.

Learn more »

Researchers discover structure of fluoride-specific ion channel

Creation of ‘atomic blueprint’ is a biological novelty

The original Brandeis NOW press release by Kimm Fesenmaier can be read here

Fluoride protects our teeth against cavity-causing bacteria by making our teeth stronger. But what if we could find a way to trap fluoride ions (the negatively charged form of the chemical element fluorine) inside bacteria? At the right concentration, fluoride ions are highly toxic to bacteria, wreaking havoc on their proteins and disrupting critical cellular functions. Bacteria, however, can fight back, exporting the toxic fluoride ions out using specialized proteins called fluoride-specific ion channels.

How these proteins remove fluoride ions from the cell is poorly understand. To glimpse into the inner workings of these proteins, researchers in Christopher Miller’s lab at Brandeis University in collaboration with Simon Newstead at the University of Oxford have determined the structure of one such fluoride-specific ion channel from the Bordetella pertussis bacteria called Bpe.

In a paper published by Nature on Sept. 7, lead author Randy Stockbridge, a post-doctorate fellow in Miller’s lab, and colleagues used a technique called X-ray crystallography to obtain an “atomic blueprint” illustrating the arrangement of the amino acids that make up Bpe. The details provide important insight into how Bpe exports fluoride out of the cell. Intriguingly, the schematics also point out potential weaknesses in Bpe that could be exploited to trap fluoride inside bacteria.

Based on the blueprint, the Bpe fluoride-specific ion channel resembles an hourglass and is actually composed of two Bpe protein molecules. At the center where the hourglass constricts is a sodium ion that may act like a pin that fastens the two Bpe proteins together. However, rather than having a central pore like an hourglass, the arrangement of the two Bpe molecules forms two parallel tunnels through which fluoride ions could flow. The blueprint also helps explain why Bpe only exports fluoride; the tunnels are just the right size for fluoride ions, but are too narrow for the biologically abundant chloride ion, fluoride’s larger but chemically similar cousin.

Notably, the researchers observed two unidentifiable “hazy shadows” in each tunnel, which they concluded were fluoride ions. First, many of the amino acids along the walls of each channel that protrude toward the shadows are chemically attracted to fluoride ions. Consistently, when the researchers mutated some of these amino acids to change their chemical properties, Bpe’s ability to export fluoride ions out of the bacteria was dramatically reduced. The researchers also studied the structure of a related fluoride-specific ion channel, Ec2, and found similar hazy shadows in its tunnels.

The researchers also noted a peculiar feature of Bpe that has implications for how the protein moves fluoride out. At one point in each of the tunnels, the side chain, or chemical appendage, of a particular amino acid protrudes inward, contacts the fluoride ion, and impedes its path to the exit. The side chain can swivel though, so it may be that the fluoride ion grasps it as though it were a turnstile and is then pulled to the other side when the side chain rotates.

Armed with Bpe’s blueprints, researchers can exploit structural weaknesses and develop strategies that kill bacteria by preventing fluoride from being moved out. Chemical compounds could be designed that pull the sodium ion pin and dismantle Bpe or that lock the turnstile causing a fluoride traffic jam that backs up into the cell.

In addition to Stockbridge, Miller and Newstead, the paper’s other authors are Ludmila Kolmakova-Partensky, Tania Shane, Akiko Koide and Shohei Koide.

The research was supported in part by a Wellcome Trust Investigator Award and grants from the National Institutes of Health (NIH) (RO1-GM107023 and U54-GM087519). Stockbridge also was supported by an NIH grant (K99-GM-111767). Miller is a Howard Hughes Medical Investigator.

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