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Message boards : News : New paper: Small Molecule Modulation of Intrinsically Disordered Proteins Using Molecular Dynamics Simulations.

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Toni
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Message 55272 - Posted: 9 Sep 2020 | 9:24:39 UTC
Last modified: 9 Sep 2020 | 9:26:19 UTC

Another great GPUGRID-based work: studying the possible modulation of intrinsically disordered proteins through drugs.

Herrera-Nieto P, PĂ©rez A, De Fabritiis G, Small Molecule Modulation of Intrinsically Disordered Proteins Using Molecular Dynamics Simulations. Journal of chemical information and modeling 2020. doi:10.1021/acs.jcim.0c00381

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The extreme dynamic behavior of intrinsically disordered proteins hinders the development of drug-like compounds capable of modulating them. There are several examples of small molecules that specifically interact with disordered peptides. However, their mechanisms of action are still not well understood. Here, we use extensive molecular dynamics simulations combined with adaptive sampling algorithms to perform free ligand binding studies in the context of intrinsically disordered proteins. We tested this approach in the system composed by the D2 sub-domain of the disordered protein p27 and the small molecule SJ403. The results show several protein–ligand bound states characterized by the establishment of a loosely oriented interaction mediated by a limited number of contacts between the ligand and critical residues of p27. Finally, protein conformations in the bound state are likely to be explored by the isolated protein too, therefore supporting a model where the addition of the small molecule restricts the available conformational space.

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Message 55273 - Posted: 9 Sep 2020 | 10:08:56 UTC - in response to Message 55272.

Wow Toni :) That's quite the pace GPU Grid is showing off at the moment. Awesome that within the last 2 months there has been a lot of activity on paper publishing. We're up to 5 papers now in only 6 weeks!

Short question: When were the batches run that resulted in this paper? I am asking as the field WU tag right below the headline of the respective paper on the science page has been empty for the most recent ones. Thanks!

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Message boards : News : New paper: Small Molecule Modulation of Intrinsically Disordered Proteins Using Molecular Dynamics Simulations.