Enhancements to the Rosetta Energy Function Enable Improved Identification of Small Molecules that Inhibit Protein-Protein Interactions.
PLoS One
; 10(10): e0140359, 2015.
Article
em En
| MEDLINE
| ID: mdl-26484863
ABSTRACT
Protein-protein interactions are among today's most exciting and promising targets for therapeutic intervention. To date, identifying small-molecules that selectively disrupt these interactions has proven particularly challenging for virtual screening tools, since these have typically been optimized to perform well on more "traditional" drug discovery targets. Here, we test the performance of the Rosetta energy function for identifying compounds that inhibit protein interactions, when these active compounds have been hidden amongst pools of "decoys." Through this virtual screening benchmark, we gauge the effect of two recent enhancements to the functional form of the Rosetta energy function the new "Talaris" update and the "pwSHO" solvation model. Finally, we conclude by developing and validating a new weight set that maximizes Rosetta's ability to pick out the active compounds in this test set. Looking collectively over the course of these enhancements, we find a marked improvement in Rosetta's ability to identify small-molecule inhibitors of protein-protein interactions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bibliotecas de Moléculas Pequenas
/
Descoberta de Drogas
/
Mapas de Interação de Proteínas
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos