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.

Preview

Text Townsend-Nicholson_Chapter20-Arrestin-Rhodopsin-FMO-v5.1.pdf - Accepted Version Download (654kB) | Preview

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.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item