Discovery of allosteric binding sites by crystallographic fragment screening.
Curr Opin Struct Biol
; 65: 209-216, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-1065572
ABSTRACT
Understanding allosteric regulation of proteins is fundamental to our study of protein structure and function. Moreover, allosteric binding pockets have become a major target of drug discovery efforts in recent years. However, even though the function of almost every protein can be influenced by allostery, it remains a challenge to discover, rationalise and validate putative allosteric binding pockets. This review examines how the discovery and analysis of putative allosteric binding sites have been influenced by the availability of centralised facilities for crystallographic fragment screening, along with newly developed computational methods for modelling low occupancy features. We discuss the experimental parameters required for success, and how new methods could influence the field in the future. Finally, we reflect on the general problem of how to translate these findings into actual ligand development programs.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Proteins
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Curr Opin Struct Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
J.sbi.2020.08.004
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