Dears,

we added a badge for a (not-so-recent-any-more) paper Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity. The abstract is here and the text is open-access.

It is interesting because it provides evidence about the kinetics (i.e., transient conformational changes) incurred by the µ-opioid receptor (MOR) upon binding to drugs. MOR is part of the large and important GPCR protein family, which is targeted by approx ~30% of the current drugs.

Abhijeet Kapoor, Gerard Martinez-Rosell, Davide Provasi, Gianni de Fabritiis & Marta Filizola
Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity
Scientific Reports volume 7, Article number: 11255 (2017)

While the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation.

Thanks for this unexpected badge! And thanks for the heads-up, Toni!

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[CSF] Thomas H.V. Dupont
Founder of the team CRUNCHERS SANS FRONTIERES 2.0
www.crunchersansfrontieres

Here's the top-20 list

rank	userid	credit
		
1	358176	849294000
2	93201	551227600
3	14310	474189150
4	101936	362332900
5	100499	347974625
6	126468	296886825
7	25378	293348100
8	68549	280535475
9	9991	241162075
10	36684	200853150
11	28899	169370700
12	69336	156029300
13	116931	153182050
14	109388	148951850
15	125700	133169950
16	31053	133007250
17	59165	131014175
18	62432	118038850
19	73475	116859275
20	97126	108358200

Thanks Toni!

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[CSF] Thomas H.V. Dupont
Founder of the team CRUNCHERS SANS FRONTIERES 2.0
www.crunchersansfrontieres

Here's the top-20 list

rank | ----credits---- | user
_1__| 849,294,000 | Syracuse University
_2__| 551,227,600 | RaymondFO*
_3__| 474,189,150 | Retvari Zoltan
_4__| 362,332,900 | Rion Family
_5__| 347,974,625 | jjch
_6__| 296,886,825 | Gunde
_7__| 293,348,100 | Stoneageman
_8__| 280,535,475 | AND
_9__| 241,162,075 | Beyond
10__| 200,853,150 | Grzegorz Roman Granowski
11__| 169,370,700 | Bob Deller
12__| 156,029,300 | neilp62
13__| 153,182,050 | Nicolas CAZIN
14__| 148,951,850 | caffeineyellow5
15__| 133,169,950 | Erich56
16__| 133,007,250 | Thomas M. Taylor
17__| 131,014,175 | Bikermatt
18__| 118,038,850 | om
19__| 116,859,275 | Viktor Svantner
20__| 108,358,200 | captainjack

I've made the toplist human readable.
I hope I've corrected all typos.

Thanks Zoltan and congrats for your 3rd place!

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[CSF] Thomas H.V. Dupont
Founder of the team CRUNCHERS SANS FRONTIERES 2.0
www.crunchersansfrontieres