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ToniVolunteer moderator Project administrator Project developer Project tester Project scientist Send message
Joined: 9 Dec 08 Posts: 1006 Credit: 5,068,599 RAC: 0 Level
![Serine - More than 5M credits Ser](img/badges/aa/badge_ser.png) Scientific publications
![Top 25% (19th/113) contribution to Giorgino et al, Comp. Phys. Commun. 2010 wat](img/badges/papers/badge_pub_ruby.png) ![Top 50% (3115th/9662) contribution to Buch et al, J. Chem. Theory Comput. 2011 wat](img/badges/papers/badge_pub_gold.png) ![Top 90% (2432nd/3113) contribution to Giorgino et al, J. Chem. Theory Comput, 2012 wat](img/badges/papers/badge_pub_bronze.png) ![Top 50% (1812th/4815) contribution to Stanley et al., Sci Rep 2016 wat](img/badges/papers/badge_pub_gold.png) |
Here we studied a possible mode of action of NF023, a molecule which disrupts some protein-protein interactions (cIAP-TRAF) misregulated in cancer. The molecule is very charged and flexible, so classical docking studies aren't up to a full modeling... but large-scale MD powered by GPUGRID is.
Cossu F, Sorrentino L, Fagnani E, Zaffaroni M, Milani M, Giorgino T, Mastrangelo E. Computational and experimental characterization of NF023, a candidate anticancer compound inhibiting cIAP2/TRAF2 assembly. J Chem Inf Model. 2020 Aug 21 doi:10.1021/acs.jcim.0c00518
Protein-protein interactions are the basis of many important physiological processes, and are currently promising, yet difficult, targets for drug discovery. In this context, inhibitors of apoptosis (IAPs)-mediated interactions are pivotal for cancer cell survival; the interaction of the BIR1 domain of cIAP2 with TRAF2 was shown to lead the recruitment of cIAPs to the TNF-receptor, promoting the activation of NF-κB survival pathway. In this work, using a combined in silico-in vitro approach we identified a drug-like molecule, NF023, able to disrupt cIAP2 interaction with TRAF2. We demonstrated in vitro its ability to interfere with the assembly of the cIAP2-BIR1/TRAF2 complex and performed a thorough characterization of the compound’s mode of action through 248 parallel unbiased molecular dynamics simulations of 300 ns (totaling almost 75 µs of all-atom sampling), which identified multiple binding modes to the BIR1 domain of cIAP2 via clustering and ensemble docking. NF023 is, thus, a promising protein-protein interaction disruptor, representing a starting point to develop modulators of NF-κB-mediated cell survival in cancer. This study represents a model-procedure that shows the use of large-scale molecular dynamics methods to typify promiscuous interactors.
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rod4x4Send message
Joined: 4 Aug 14 Posts: 266 Credit: 2,219,935,054 RAC: 0 Level
![Phenylalanine - More than 2B credits Phe](img/badges/aa/badge_phe.png) Scientific publications
![Top 25% (768th/3183) contribution to Lauro et al., JCIM 2014 wat](img/badges/papers/badge_pub_ruby.png) ![Top 10% (340th/4128) contribution to Ferruz et al., Sci Rep 2016 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (149th/4730) contribution to Noe et al., Nat Chem 2017 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (133rd/1348) contribution to Doerr et al, JCTC 2017 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (134th/4634) contribution to Martinez-Rosell et al, JCIM 2018 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (152nd/1656) contribution to Kapoor et al., Sci Rep 2017 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (144th/1885) contribution to Ferruz et al., Sci Rep 2018 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (51st/672) contribution to Martinez-Rosell et al, JCIM 2020 wat](img/badges/papers/badge_pub_emerald.png) ![Top 10% (150th/1541) contribution to Rodriguez-Espigares et al., Nat Meth 2020 wat](img/badges/papers/badge_pub_emerald.png) ![Top 1% (35th/6232) contribution to Herrera-Nieto et al, JCIM 2020 wat](img/badges/papers/badge_pub_sapphire.png) |
Nice!!
Always good to see results from the hard workng team at Gpugrid.
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Nice!!
Always good to see results from the hard workng team at Gpugrid.
+1 :) Thanks Toni!
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[CSF] Thomas H.V. Dupont
Founder of the team CRUNCHERS SANS FRONTIERES 2.0
www.crunchersansfrontieres |
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Keith Myers Send message
Joined: 13 Dec 17 Posts: 1313 Credit: 6,015,017,459 RAC: 9,824,344 Level
![Tyrosine - More than 5B credits Tyr](img/badges/aa/badge_tyr.png) Scientific publications
![Top 10% (64th/1022) contribution to Wang et al., ACS Cent. Sci. 2019 wat](img/badges/papers/badge_pub_emerald.png) ![Top 50% (273rd/672) contribution to Martinez-Rosell et al, JCIM 2020 wat](img/badges/papers/badge_pub_gold.png) ![Top 75% (1040th/1541) contribution to Rodriguez-Espigares et al., Nat Meth 2020 wat](img/badges/papers/badge_pub_silver.png) ![Top 10% (413th/6232) contribution to Herrera-Nieto et al, JCIM 2020 wat](img/badges/papers/badge_pub_emerald.png) ![Top 100% (294th/315) contribution to Cossu et al, JCIM 2020 wat](img/badges/papers/badge_pub_white.png) |
[quote]Nice!!
Always good to see results from the hard workng team at Gpugrid.
+1 :) Thanks Toni![/quote
+100
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I'm wondering why I'm not getting any of these in my "Scientific Publications"... all I have so far is "579th/672 Martinez-Rosell et al, JCIM 2020" but I've been in the top five by production since that paper, and newer ones I see in others' publications lists haven't appeared.
Just my usual luck I guess. :^) |
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ToniVolunteer moderator Project administrator Project developer Project tester Project scientist Send message
Joined: 9 Dec 08 Posts: 1006 Credit: 5,068,599 RAC: 0 Level
![Serine - More than 5M credits Ser](img/badges/aa/badge_ser.png) Scientific publications
![Top 25% (19th/113) contribution to Giorgino et al, Comp. Phys. Commun. 2010 wat](img/badges/papers/badge_pub_ruby.png) ![Top 50% (3115th/9662) contribution to Buch et al, J. Chem. Theory Comput. 2011 wat](img/badges/papers/badge_pub_gold.png) ![Top 90% (2432nd/3113) contribution to Giorgino et al, J. Chem. Theory Comput, 2012 wat](img/badges/papers/badge_pub_bronze.png) ![Top 50% (1812th/4815) contribution to Stanley et al., Sci Rep 2016 wat](img/badges/papers/badge_pub_gold.png) |
The process between calculations and scientific publication is quite involved. The lag between getting results, analysis, authoring, iterating, submitting the paper, reviewing it, and so on may easily take years.
Also, some papers are based on relatively few WUs, so only a few random crunchers get them. |
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Thank you for the response! That answers it quite nicely. :^) |
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