eprintid: 10093312
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/09/33/12
datestamp: 2020-03-13 12:38:15
lastmod: 2021-12-13 23:32:14
status_changed: 2020-03-13 12:38:15
type: article
metadata_visibility: show
creators_name: Heifetz, A
creators_name: James, T
creators_name: Southey, M
creators_name: Morao, I
creators_name: Fedorov, DG
creators_name: Bodkin, MJ
creators_name: Townsend-Nicholson, A
title: Analyzing GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G03
keywords: Chemical interactions, Computational, Computer-aided drug design (CADD), Drugs, Fragment molecular orbital method (FMO), G-protein-coupled receptors (GPCR), General atomic and molecular electronic structure system (GAMESS), Modelling, Pair interaction energy (PIE), Pair interaction energy decomposition analysis (PIEDA), Quantum mechanics (QM), Receptor, Structure-based drug design (SBDD)
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: G-protein-coupled receptors (GPCRs) have enormous physiological and biomedical importance, and therefore it is not surprising that they are the targets of many prescribed drugs. Further progress in GPCR drug discovery is highly dependent on the availability of protein structural information. However, the ability of X-ray crystallography to guide the drug discovery process for GPCR targets is limited by the availability of accurate tools to explore receptor-ligand interactions. Visual inspection and molecular mechanics approaches cannot explain the full complexity of molecular interactions. Quantum mechanics (QM) approaches are often too computationally expensive to be of practical use in time-sensitive situations, but the fragment molecular orbital (FMO) method offers an excellent solution that combines accuracy, speed, and the ability to reveal key interactions that would otherwise be hard to detect. Integration of GPCR crystallography or homology modelling with FMO reveals atomistic details of the individual contributions of each residue and water molecule toward ligand binding, including an analysis of their chemical nature. Such information is essential for an efficient structure-based drug design (SBDD) process. In this chapter, we describe how to use FMO in the characterization of GPCR-ligand interactions.
date: 2020-02-04
date_type: published
official_url: https://doi.org/10.1007/978-1-0716-0282-9_11
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1749280
doi: 10.1007/978-1-0716-0282-9_11
lyricists_name: Townsend-Nicholson, Andrea
lyricists_id: ATOWN70
actors_name: Stacey, Thomas
actors_id: TSSTA20
actors_role: owner
full_text_status: public
publication: Methods in Molecular Biology
volume: 2114
pagerange: 163-175
event_location: United States
citation:        Heifetz, A;    James, T;    Southey, M;    Morao, I;    Fedorov, DG;    Bodkin, MJ;    Townsend-Nicholson, A;      (2020)    Analyzing GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method.                   Methods in Molecular Biology , 2114    pp. 163-175.    10.1007/978-1-0716-0282-9_11 <https://doi.org/10.1007/978-1-0716-0282-9_11>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10093312/3/Townsend-Nicholson_Chapter11-GPCR-ligand-interactions-with-FMO-v4.0.pdf