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Characterizing Rhodopsin-Arrestin Interactions with the Fragment Molecular Orbital (FMO) Method

Heifetz, A; Townsend-Nicholson, A; (2020) Characterizing Rhodopsin-Arrestin Interactions with the Fragment Molecular Orbital (FMO) Method. Methods in Molecular Biology , 2114 pp. 177-186. 10.1007/978-1-0716-0282-9_12. Green open access

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Abstract

Arrestin binding to G protein-coupled receptors (GPCRs) plays a vital role in receptor signaling. Recently, the crystal structure of rhodopsin bound to activated visual arrestin was resolved using XFEL (X-ray free electron laser). However, even with the crystal structure in hand, our ability to understand GPCR-arrestin binding is limited by the availability of accurate tools to explore receptor-arrestin interactions. We applied fragment molecular orbital (FMO) method to explore the interactions formed between the residues of rhodopsin and arrestin. FMO enables ab initio approaches to be applied to systems that conventional quantum mechanical (QM) methods would be too compute-expensive. The FMO calculations detected 35 significant interactions involved in rhodopsin-arrestin binding formed by 25 residues of rhodopsin and 28 residues of arrestin. Two major regions of interaction were identified: at the C-terminal tail of rhodopsin (D330-S343) and where the "finger loop" (G69-T79) of arrestin directly inserts into rhodopsin active core. Out of these 35 interactions, 23 were mainly electrostatic and 12 hydrophobic in nature.

Type: Article
Title: Characterizing Rhodopsin-Arrestin Interactions with the Fragment Molecular Orbital (FMO) Method
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-1-0716-0282-9_12
Publisher version: https://doi.org/10.1007/978-1-0716-0282-9_12
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Arrestin, Biased ligands, Chemical interactions, Fragment molecular orbital method (FMO), G protein-coupled receptors (GPCR), Pair interaction energy (PIE), Quantum mechanics (QM), Rhodopsin, Signaling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10093315
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