Mapping Ligand-Shape Space for Protein-Ligand Systems: Distinguishing Key-in-Lock and Hand-in-Glove Proteins.
J Chem Inf Model
; 61(4): 1859-1874, 2021 04 26.
Article
en En
| MEDLINE
| ID: mdl-33755448
ABSTRACT
Many of the recently developed methods to study the shape of molecules permit one conformation of one molecule to be compared to another conformation of the same or a different molecule a relative shape. Other methods provide an absolute description of the shape of a conformation that does not rely on comparisons or overlays. Any absolute description of shape can be used to generate a self-organizing map (shape map) that places all molecular shapes relative to one another; in the studies reported here, the shape fingerprint and ultrafast shape recognition methods are employed to create such maps. In the shape maps, molecules that are near one another have similar shapes, and the maps for the 102 targets in the DUD-E set have been generated. By examining the distribution of actives in comparison with their physical-property-matched decoys, we show that the proteins of key-in-lock type (relatively rigid receptor and ligand) can be distinguished from those that are more of a hand-in-glove type (more flexible receptor and ligand). These are linked to known differences in protein flexibility and binding-site size.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Algoritmos
/
Proteínas
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido