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Message boards : News : (Another) New publication: optimized methods to compute binding free energies

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Message 21183 - Posted: 13 May 2011 | 12:23:21 UTC

May the party continue with our second publication from GPUGRID computations! The work, also to be published at the Journal of Chemical Theory and Computation, presents the optimization of a previously developed protocol to accurately compute binding affinities between proteins and small peptides. Such methods may be employed in the future for drug design studies. WUs related to this publication are all the *pYEEI*. Congratulations to you all!
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)

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Message 21193 - Posted: 15 May 2011 | 18:58:43 UTC - in response to Message 21183.

Abstract: The prediction of protein–ligand binding free energies is an important goal of computational biochemistry, yet accuracy, reproducibility, and cost remain a problem. Nevertheless, these are essential requirements for computational methods to become standard binding prediction tools in discovery pipelines. Here, we present the results of an extensive search for an optimal method based on an ensemble of umbrella sampling all-atom molecular simulations tested on the phosphorylated tetrapeptide, pYEEI, binding to the SH2 domain, resulting in an accurate and converged binding free energy of −9.0 ± 0.5 kcal/mol (compared to an experimental value of −8.0 ± 0.1 kcal/mol). We find that a minimum of 300 ns of sampling is required for every prediction, a target easily achievable using new generation accelerated MD codes. Convergence is obtained by using an ensemble of simulations per window, each starting from different initial conformations, and by optimizing window-width, orthogonal restraints, reaction coordinate harmonic potentials, and window-sample time. The use of uncorrelated initial conformations in neighboring windows is important for correctly sampling conformational transitions from the unbound to bound states that affect significantly the precision of the calculations. This methodology thus provides a general recipe for reproducible and practical computations of binding free energies for a class of semirigid protein–ligand systems, within the limit of the accuracy of the force field used.

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Message 21194 - Posted: 16 May 2011 | 1:19:54 UTC

Congratulations!

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Message 21203 - Posted: 17 May 2011 | 9:46:24 UTC - in response to Message 21193.
Last modified: 17 May 2011 | 9:47:40 UTC

I would expect to see plenty of references to this paper in the future ;)

- Well done guys

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Message 21299 - Posted: 4 Jun 2011 | 10:34:35 UTC - in response to Message 21183.

May the party continue with our second publication from GPUGRID computations! The work, also to be published at the Journal of Chemical Theory and Computation, presents the optimization of a previously developed protocol to accurately compute binding affinities between proteins and small peptides. Such methods may be employed in the future for drug design studies. WUs related to this publication are all the *pYEEI*. Congratulations to you all!
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)


You guys don't seem to get a mention on the main BOINC site in the news. Do you mention it to Dr Anderson? He could then add it as the other projects seem to mention their successes and milestones. A bit of promotion for the project wouldn't go astray.
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Message 21300 - Posted: 4 Jun 2011 | 13:20:32 UTC - in response to Message 21299.
Last modified: 4 Jun 2011 | 13:32:15 UTC

http://boinc.berkeley.edu/ - News, right hand side.

Also worth noting is that Boinc 6.12.x has a Notices tab that can be used by projects for announcements.
They typically contain a title, brief message and a URL link for further information.
Project changes, events and papers are common entries.

At the minute I think you only get messages from projects that you are attached to, but I don't recall seeing any from GPUGrid.
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Message 21303 - Posted: 5 Jun 2011 | 0:52:34 UTC - in response to Message 21300.

http://boinc.berkeley.edu/ - News, right hand side.


Yes thats the one. No mention of GPUgrid. Various other projects and milestones, but nothing about GPUgrid.


Also worth noting is that Boinc 6.12.x has a Notices tab that can be used by projects for announcements.
They typically contain a title, brief message and a URL link for further information.
Project changes, events and papers are common entries.

At the minute I think you only get messages from projects that you are attached to, but I don't recall seeing any from GPUGrid.


The project developers would need to update the server side software so they can use them.
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Message 21533 - Posted: 23 Jun 2011 | 10:11:15 UTC

It seems we've (GPUgrid that is) finally got a mention on the BOINC website in the news section. Posted 2 days ago...
New publications from GPUGRID.net

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Message boards : News : (Another) New publication: optimized methods to compute binding free energies