UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Characterizing Protein-Protein Interactions with the Fragment Molecular Orbital Method

Heifetz, A; Sladek, V; Townsend-Nicholson, A; Fedorov, DG; (2020) Characterizing Protein-Protein Interactions with the Fragment Molecular Orbital Method. Methods in Molecular Biology , 2114 pp. 187-205. 10.1007/978-1-0716-0282-9_13. Green open access

[thumbnail of Townsend-Nicholson_Chapter13-v8.0.pdf]
Preview
Text
Townsend-Nicholson_Chapter13-v8.0.pdf - Accepted Version

Download (930kB) | Preview

Abstract

Proteins are vital components of living systems, serving as building blocks, molecular machines, enzymes, receptors, ion channels, sensors, and transporters. Protein-protein interactions (PPIs) are a key part of their function. There are more than 645,000 reported disease-relevant PPIs in the human interactome, but drugs have been developed for only 2% of these targets. The advances in PPI-focused drug discovery are highly dependent on the availability of structural data and accurate computational tools for analysis of this data. Quantum mechanical approaches are often too expensive computationally, 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. FMO provides essential information for PPI drug discovery, namely, identification of key interactions formed between residues of two proteins, including their strength (in kcal/mol) and their chemical nature (electrostatic or hydrophobic). In this chapter, we have demonstrated how three different FMO-based approaches (pair interaction energy analysis (PIE analysis), subsystem analysis (SA) and analysis of protein residue networks (PRNs)) have been applied to study PPI in three protein-protein complexes.

Type: Article
Title: Characterizing Protein-Protein Interactions with the Fragment Molecular Orbital Method
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-1-0716-0282-9_13
Publisher version: https://doi.org/10.1007/978-1-0716-0282-9_13
Language: English
Additional information: This version is the accepted manuscript version. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Binding energy, Desolvation penalty, Efficiency centrality, FMO, Fragment molecular orbital, Molecular recognition, Network analysis of protein residue networks, PIE, PIE-PRN, PPI, PRN, Pair interaction energy, Protein residue networks, Protein-protein interactions, QM, Quantum mechanics, Subsystem analysis
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/10093311
Downloads since deposit
298Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item