Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies.
Int J Mol Sci
; 22(22)2021 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-34830201
ABSTRACT
The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein-ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein-ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Simulación del Acoplamiento Molecular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Año:
2021
Tipo del documento:
Article