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Characterization of...
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Kuang, GuanglinKTH,Teoretisk kemi och biologi,Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.
(author)
Characterization of the binding mode of the PET tracer [18F]ASEM to a chimera structure of the α7 nicotinic acetylcholine receptor
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017
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Royal Society of Chemistry,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-207402
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-207402URI
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https://doi.org/10.1039/c7ra00496fDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:135687740URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-322119URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20170601
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The α7 nicotinic acetylcholine receptor (α7-nAChR) is assumed to be implicated in a variety of neurological disorders, such as schizophrenia and Alzheimer's disease (AD). The progress of these disorders can be studied through imaging α7-nAChR with positron emission tomography (PET). [18F]ASEM is a novel and potent α7-nAChR PET radioligand showing great promise in recent tests. However, the mechanism of the molecular interaction between [18F]ASEM and α7-nAChR is still unclear. In this paper, the binding profile of [18F]ASEM to a chimera structure of α7-nAChR was investigated with molecular docking, molecular dynamics, and metadynamics simulation methods. We found that [18F]ASEM binds at the same site as the crystallized agonist epibatidine but with a different binding mode. The dibenzo[b,d]thiophene ring has a different orientation compared to the pyridine ring of epibatidine and has van der Waals interactions with residues from loop C on one side and π-π stacking interaction with Trp53 on the other side. The conformation of Trp53 was found to have a great impact on the binding of [18F]ASEM. Six binding modes in terms of the side chain dihedral angles χ1 and χ2 of Trp53 were discovered by metadynamics simulation. In the most stable binding mode, Trp53 adopts a different conformation from that in the crystalline structure and has a rather favorable π-π stacking interaction with [18F]ASEM. We believe that these discoveries can be valuable for the development of novel PET radioligands.
Subject headings and genre
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NATURVETENSKAP Kemi hsv//swe
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NATURAL SCIENCES Chemical Sciences hsv//eng
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Binding energy
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Dihedral angle
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Molecular dynamics
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Neurodegenerative diseases
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Positron emission tomography
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Van der Waals forces
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Alzheimer's disease
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Crystalline structure
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Metadynamics simulations
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Molecular docking
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Neurological disorders
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Nicotinic acetylcholine receptors
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Positron emission tomography (PET)
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Van Der Waals interactions
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Bins
Added entries (persons, corporate bodies, meetings, titles ...)
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Zhou, Yang,1986-KTH,Teoretisk kemi och biologi,Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1qoay2o
(author)
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Zou, RongfengKTH,Teoretisk kemi och biologi,Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1808q2l
(author)
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Halldin, C.Karolinska Institutet,Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
(author)
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Nordberg, A.Karolinska Institutet,Karolinska Univ Hosp, Ctr Alzheimer Res Translat Alzheimer Neurobiol, Dept Neurobiol Care Sci & Soc, S-14186 Huddinge, Sweden.
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Långström, BengtUppsala universitet,Organisk kemi(Swepub:uu)benglang
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Ågren, HansKTH,Teoretisk kemi och biologi,Siberian Federal University, Russian Federation,Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.;Siberian Fed Univ, Inst Nanotechnol Spect & Quantum Chem, Svobodny Pr 79, Krasnoyarsk 660041, Russia.(Swepub:kth)u1l2s96v
(author)
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Tu, YaoquanKTH,Teoretisk kemi och biologi,Royal Inst Technol KTH, AlbaNova Univ Ctr, Sch Biotechnol, Div Theoret Chem & Biol, S-10691 Stockholm, Sweden.(Swepub:kth)u1kuh2ie
(author)
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KTHTeoretisk kemi och biologi
(creator_code:org_t)
Related titles
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In:RSC Advances: Royal Society of Chemistry7:32, s. 19787-197932046-2069
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