Archive by date: June

First Frontiers in Membrane Protein Structural Dynamics Conference was a success

Dorothee Kern, Brandeis University and External Advisory Committee Member

On May 3rd and 4th, the Membrane Protein Structural Dynamics Consortium (MPSDC) held its first Frontiers in Membrane Protein Structural Dynamics conference. The conference consisted of scientific sessions and poster presentations, and featured both Consortium members and external invitees. Attendance was open to the public took place within the context of our 3rd Annual MPSDC Meeting, where all members, NIH representatives and our External Advisory Committee participated. Prior to the conference, the MPSDC’s Computational Modeling Core hosted a NAMD/VMD workshop and a mini-symposium concerning the latest advances in membrane protein modeling.

Miguel Holmgren, NINDS and collaborator in Bridge 1: Conformational Transitions in P-class ATPases

Both the conference and CMC events were very well attended and enabled extensive conversations surrounding the topic of cutting edge advances and scientific methods in the field of membrane protein dynamics, as well as ways to resolve current roadblocks. The conference was able to hit a high note in bringing together the issues and ideas most relevant to the key goals of the consortium both in the present and in the future. Chris Ahern of the University of British Columbia and MPSDC Associate Member noted afterwards that it was probably one of the best meetings he’s been to, “primarily because of the quality of the science that’s being done, as well as the excitement and eagerness of people to cooperate.”

José Faraldo-Gómez, Max Planck Institute for Biophysics and MPSDC Associate Member

In the afternoon, two discussion panels were held, which themselves are in the spirit of much of the broader conversations that took place at the conference as a whole. The first panel, “Finding a common language: linking experiment and computation” was chaired by Hassane Mchaourab, and included Benoît Roux, Martin Zanni, Ivet Bahar, Dorothee Kern, and Emad Tajkhorshid as participants.

Chris Ahern, University of British Columbia and MPSDC Associate Member

The second panel was titled “Breaking the barriers of membrane protein expression and labeling” and was moderated by Robert Nakamoto. The panel included Chris Ahern, Jim Bowie, Volker Dötsch and Shohei Koide. Discussion focused on three topics: the optimal nitroxide spin probe for monitoring protein dynamics and DEER distance measurements, how to incorporate such a probe into the protein targets, and cell free synthesis of target proteins. The optimal nitroxide spin probe would be connected to the backbone by only a β carbon. Such a label can be introduced using chemical synthesis, but because most of our proteins are too large, methods for bio-incorporation of unnatural amino acid are preferred. Cell free biosynthesis systems such as those developed in the laboratory of Volker Dötsch, Goethe University, and Chris Ahern, University of British Columbia, may provide the best approaches. The Protein Core labs will explore methods for charging the non-sense tRNA by evolved tRNA synthetases or a ribozyme using technologies called the Flexizyme developed by Soga and co-workers at Tokyo University. The acylated TAG tRNA charged with the spin probe is simply added to the cell free synthesis mix. Another issue is the lability of nitoxides to reduction by ascorbic acid. We will test a variety of nitroxide spin probes, which have been reported to be relatively insensitive to reduction. Finally, we discussed specific placement of labels using synthetic binders. In particular, the synthetic 10FN3 binders, or monobodies (~93 aa, derived from a type III fibronectin domain), can mediate specific labeling of a protein and effectively attach a label or cargo to the protein target with high affinity and stability.

We’d like to thank all who attended and partook in the discussions. By all accounts, it is hard to think of a better outcome for the conference and accompanying events, and we look forward to hosting another meeting in two years.

Below is a gallery displaying photos of the conference. You can either scroll through the photos here or visit the set on Flickr. We’ve also made available several brief audio interviews with attendees of the conference, to be found in the margins of the body of this post.

New Continuum-Molecular Dynamics (CTMD) software made available by Computational Modeling Core

The membrane environment is a key determinant of function and/or organization of membrane proteins. It is essential for the activities of the Consortium to have access to quantitative information about the characteristics and energetics of membrane-protein interactions. For multi-segment transmembrane proteins in particular, such characterization is complicated by the different hydrophobic thicknesses of the component transmembrane segments and the radially non-uniform hydrophobic interface created between the membrane and the protein. A hybrid Continuum-Molecular Dynamics (CTMD) approach to compute membrane deformations profiles around multi-segment proteins and corresponding energetics was recently published [Sayan Mondal, George Khelashvili, Jufang Shan, Olaf Andersen, Harel Weinstein (2011), Biophysical J (101): 2092-2101; link]. This stand-alone application implements the CTMD approach.

Protocol for the 3D-CTMD approach, illustrated for rhodopsin in a diC14:1PC lipid bilayer (Mondal et al., BJ 2011). Click to enlarge and learn more.

The CTMDapp software calculates the deformation profiles of the bilayer and the free energy cost of the membrane deformation around multi-segment transmembrane proteins, taking into account the radially non-uniform hydrophobic surface of the protein. As the primary input it requires a molecular dynamics trajectory of a multi-segment, transmembrane protein embedded in a bilayer.

To allow for calculations without a molecular dynamics input, the CTMDapp software also implements a simplified version of the CTMD method that can assess the radial asymmetry of the membrane-protein interface for a particular protein structure at an approximate level.

Methodological details can be found in the original paper (Mondal et al., BJ 2011). In addition, the application is documented with brief usage notes at every step and generates diagnostic intermediate output.

Download the software:

For the Windows version, clicking on the downloadable .exe file will directly launch the Matlab Component Runtime (MCR) installation process and extract the app executable. For the Mac version, the MCR must be installed first by opening MCRinstaller.dmg in the folder. This is a one-time installation, after which CTMDapp can be launched. The Unix version requires an interface like Xwin along with a script setting proper paths.

The software was written by Sayan Mondal ( in the Harel Weinstein ( lab at Weill Cornell Medical College, Cornell University. Please feel free to contact us with questions and suggestions about the software.

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