000873887 001__ 873887
000873887 005__ 20240625095126.0
000873887 037__ $$aFZJ-2020-01077
000873887 041__ $$aEnglish
000873887 1001_ $$0P:(DE-Juel1)169313$$aMaggi, Luca$$b0$$eCorresponding author
000873887 245__ $$aModeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960
000873887 260__ $$aMittweida$$c2020
000873887 3367_ $$0PUB:(DE-HGF)25$$2PUB:(DE-HGF)$$aPreprint$$bpreprint$$mpreprint$$s1581923356_18672
000873887 3367_ $$2ORCID$$aWORKING_PAPER
000873887 3367_ $$028$$2EndNote$$aElectronic Article
000873887 3367_ $$2DRIVER$$apreprint
000873887 3367_ $$2BibTeX$$aARTICLE
000873887 3367_ $$2DataCite$$aOutput Types/Working Paper
000873887 520__ $$aAllosteric modulation is involved in a plethora of diverse protein functions, which are fundamental for cells’ life. This phenomenon can be thought as communication between two topographically distinct site of a protein structure. How this communication occurs is still matter of debate. Many different descriptions have been presented so far. Here we consider a specific case where any significant conformational change is involved upon allosteric modulator binding and the phenomenon is depicted as a vibrational energy diffusion process between distant protein regions. We applied this model, by employing computational tools, to the human muscarinic receptor M2, a transmembrane protein G-protein coupled receptor known to undergo allosteric modulation whose recently X-ray structure has been recently resolved both with and without the presence of a particular allosteric modulator. Our calculations, performed on these two receptor structures, suggest that for this case the allosteric modulator modifies the energy current between functionally relevant regions of the protein; this allows to identify the main residues responsible for this modulation. These results contribute to shed light on the molecular basis of allosteric modulation and may help design new allosteric ligands.
000873887 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x0
000873887 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b1
000873887 7001_ $$0P:(DE-Juel1)145921$$aRossetti, Giulia$$b2
000873887 773__ $$0PERI:(DE-600)1474639-6$$tScientific reports$$x1430-3698$$y2020
000873887 8564_ $$uhttps://juser.fz-juelich.de/record/873887/files/Modeling_allosteric_modulation_GPCR_Luca_Maggi_Main_Text_resubmission.docx$$yRestricted
000873887 909CO $$ooai:juser.fz-juelich.de:873887$$pVDB
000873887 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)169313$$aForschungszentrum Jülich$$b0$$kFZJ
000873887 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-Juel1)169313$$aRWTH Aachen$$b0$$kRWTH
000873887 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich$$b1$$kFZJ
000873887 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-Juel1)145614$$aRWTH Aachen$$b1$$kRWTH
000873887 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145921$$aForschungszentrum Jülich$$b2$$kFZJ
000873887 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-Juel1)145921$$aRWTH Aachen$$b2$$kRWTH
000873887 9131_ $$0G:(DE-HGF)POF3-574$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vTheory, modelling and simulation$$x0
000873887 9141_ $$y2020
000873887 920__ $$lyes
000873887 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0
000873887 980__ $$apreprint
000873887 980__ $$aVDB
000873887 980__ $$aI:(DE-Juel1)IAS-5-20120330
000873887 980__ $$aUNRESTRICTED
000873887 981__ $$aI:(DE-Juel1)INM-9-20140121