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Message 21330 - Posted: 7 Jun 2011 | 7:57:01 UTC

Dear users, we are grateful to announce a new publication from GPUGRID. This time at the prestigious journal Proceedings of the National Academy of Sciences of the USA (PNAS): http://dx.doi.org/10.1073/pnas.1103547108
The work published is related to WUs tagged as *TRYP*. Thank you very much to all contributors!

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Message 21332 - Posted: 7 Jun 2011 | 12:12:33 UTC - in response to Message 21330.
Last modified: 9 Jun 2011 | 10:33:47 UTC

Hi guys, I'm not unbiased but this one is huge. Here is a press release/summary. A longer version (i.e. one that highlights the role of GPUGRID and volunteers) is under way.


A major step in molecular simulation - key to designing new drugs

Researchers at Hospital del Mar Research Institute (IMIM) and Pompeu Fabra University (UPF) have successfully reproduced and reconstructed the complete process of a small molecule binding with its target protein. IMIM and UPF are part of the VPH NoE Network and this project started as part of the VPH NoE's Seed Exemplar Project 4

This advance enables the calculation of the binding affinity and binding timescale as well as understanding the interactions established by the drug in order to act, thus moving towards safer and more efficient design of new drugs. This groundbreaking project helps show a process that was hitherto invisible and therefore unknown, and opens up a new avenue in the design of new drugs.
The binding process of a drug, usually a small molecule, to its target protein is highly dynamic and depends on interactions at a nanometric scale (billions of times smaller than a metre) and occurs at timescales of nano/micro-seconds (billions of times faster than a second). The capturing of movements of small molecules with a resolution of up to an atom is beyond current technical capabilities. However, using computer techniques, it is possible to represent the molecules at atomic scale and reproduce their movements with high mathematical precision.

Understanding how protein and molecules bind - in which the latter causes a biological response after being recognised by the former (binding) - is vitally important for the design of new drugs. Despite the progress made so far with the technique, no study had provided a complete reconstruction of the protein-ligand binding process. "The method provides not only the binding affinity and the kinetics of the reaction, but also information about the atomic resolution during the process: binding sites, transition states and metastable states are potentially useful for expanding the probability of success when designing drugs. This methodology can be directly applied to other molecular systems and is therefore of general interest in biomedical and pharmaceutical research" explains Gianni de Fabritiis, coordinator of the Computational Biophysics Laboratory of the Biomedical Computer Research Programme (GRIB) run by Hospital del Mar Research Institute (IMIM) and Pompeu Fabra University (UPF).
The researchers are now working to expand the applicability of this methodology and make better use of the computational capabilities as, in cases in which ligands are larger and more flexible and where the proteins involve more complex binding processes, greater computational effort is required.

For further information please see the reference article:
"Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations" IBuch, T Giorgino, G De Fabritiis. doi: 10.1073/pnas.1103547108

Please also note that there is a video of MD simulations of free benzamidine binding to trypsin: http://www.youtube.com/watch?v=zKNmBjqGijI&feature=youtu.be

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Message 21349 - Posted: 8 Jun 2011 | 10:09:51 UTC

Brilliant stuff! Keep up the good work, GPUGrid continues to be one of most impressive BOINC projects. Hopefully these papers get a few more people to crunch this undervalued & under-participated project.

Regards from Australia

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Message 21352 - Posted: 9 Jun 2011 | 10:33:56 UTC - in response to Message 21349.

EDIT ops, corrected link to paper.

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Message 21353 - Posted: 9 Jun 2011 | 11:36:35 UTC

It would be good if news of this paper, and some of the earlier ones, could be passed on to David Anderson for inclusion in Publications by BOINC projects. (Nothing's been added to the GPUGrid (actually, still PS3Grid) section there since some updating in March 2010).

Or, if you have publication details available in a suitable format, I can add it myself.

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Message 21355 - Posted: 9 Jun 2011 | 13:44:36 UTC - in response to Message 21353.
Last modified: 9 Jun 2011 | 13:45:41 UTC

I e-mailed David with the recent publications, but got no reply. If you could add the references, that would be great. As for the format, would it be appropriate to replicate our posts here?

Btw this is the list I sent to David


T. Giorgino and G. De Fabritiis, A high-throughput steered molecular dynamics study on the free energy profile of ion permeation through gramicidin A, in press J. Chem. Theory Comput. (2011).
http://www.gpugrid.net/forum_thread.php?id=2523

I. Buch, S. K. Sadiq and G. De Fabritiis, Optimized potential of mean force calculations of standard binding free energy, in press J. Chem. Theory Comput. (2011)
http://www.gpugrid.net/forum_thread.php?id=2524

Ignasi Buch, Toni Giorgino, and Gianni De Fabritiis Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations PNAS 2011 ; published ahead of print June 6, 2011, doi:10.1073/pnas.1103547108
http://www.gpugrid.net/forum_thread.php?id=2543

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Message 21356 - Posted: 9 Jun 2011 | 14:29:37 UTC - in response to Message 21355.

I have added it.

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Message 21357 - Posted: 9 Jun 2011 | 14:31:13 UTC - in response to Message 21355.
Last modified: 9 Jun 2011 | 14:34:08 UTC

I e-mailed David with the recent publications, but got no reply. If you could add the references, that would be great. As for the format, would it be appropriate to replicate our posts here?

Stage one complete - at least the titles are showing.

I think the form is to link to the actual published articles from that page, rather than to the project. I've failed so far to convert doi:10.1073/pnas.1103547108 into a full url - is that available yet?

By way of example, one of your previous ones was linked to http://pubs.acs.org/doi/abs/10.1021/ci900455r - that seems to be the sort of thing they like.

Edit - OK, I'll keep out of the way - best you do it yourselves.

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Message boards : News : New publication in PNAS!