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  Unraveling individual host–guest interactions in molecular recognition from first principles quantum mechanics: Insights into the nature of nicotinic acetylcholine receptor agonist binding

Beck, M. E., Riplinger, C., Neese, F., & Bistoni, G. (2021). Unraveling individual host–guest interactions in molecular recognition from first principles quantum mechanics: Insights into the nature of nicotinic acetylcholine receptor agonist binding. Journal of Computational Chemistry, 42(5), 293-302. doi:10.1002/jcc.26454.

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 Creators:
Beck, Michael Edmund1, Author
Riplinger, Christoph2, Author
Neese, Frank3, Author              
Bistoni, Giovanni4, Author              
Affiliations:
1Department Computational Life Science, Bayer AG, Division Cropscience, Monheim am Rhein, Germany, ou_persistent22              
2FAccTs GmbH, Köln, Germany, ou_persistent22              
3Research Department Neese, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_2541710              
4Research Group Bistoni, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_2541703              

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Free keywords: drug design; intermolecular interactions; local coupled cluster; local energy decomposition; molecular recognition; protein-ligand interactions
 Abstract: Drug binding to a protein target is governed by a complex pattern of noncovalent interactions between the ligand and the residues in the protein's binding pocket. Here we introduce a generally applicable, parameter‐free, computational method that allows for the identification, quantification, and analysis of the key ligand–residue interactions responsible for molecular recognition. Our strategy relies on Local Energy Decomposition analysis at the “gold‐standard” coupled cluster DLPNO‐CCSD(T) level. In the study case shown in this paper, nicotine and imidacloprid binding to the nicotinic acetylcholine receptor, our approach provides new insights into how individual amino acids in the active site determine sensitivity and selectivity of the ligands, extending and refining classical pharmacophore hypotheses. By inference, the method is applicable to any kind of host/guest interactions with potential applications in industrial biocatalysis and protein engineering.

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Language(s): eng - English
 Dates: 2020-08-282020-11-242021-02-15
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/jcc.26454
 Degree: -

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Title: Journal of Computational Chemistry
  Abbreviation : J. Comput. Chem.
Source Genre: Journal
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Publ. Info: New York : Wiley
Pages: - Volume / Issue: 42 (5) Sequence Number: - Start / End Page: 293 - 302 Identifier: ISSN: 0192-8651
CoNE: https://pure.mpg.de/cone/journals/resource/954925489848