Predictions of Backbone Dynamics in Intrinsically Disordered Proteins Using De Novo Fragment-Based Protein Structure Predictions
Abstract Intrinsically disordaered proteins (IDPs) are a prevalent phenomenon with over 30% of human proteins estimated to have long disordered regions. Computational methods are widely used to study IDPs, however, nearly all treat disorder in a binary fashion, not accounting for the structural hete...
Guardado en:
| Autores principales: | , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/aaef04bc9a334c4280f7d5ac3c2199e0 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | Abstract Intrinsically disordaered proteins (IDPs) are a prevalent phenomenon with over 30% of human proteins estimated to have long disordered regions. Computational methods are widely used to study IDPs, however, nearly all treat disorder in a binary fashion, not accounting for the structural heterogeneity present in disordered regions. Here, we present a new de novo method, FRAGFOLD-IDP, which addresses this problem. Using 200 protein structural ensembles derived from NMR, we show that FRAGFOLD-IDP achieves superior results compared to methods which can predict related data (NMR order parameter, or crystallographic B-factor). FRAGFOLD-IDP produces very good predictions for 33.5% of cases and helps to get a better insight into the dynamics of the disordered ensembles. The results also show it is not necessary to predict the correct fold of the protein to reliably predict per-residue fluctuations. It implies that disorder is a local property and it does not depend on the fold. Our results are orthogonal to DynaMine, the only other method significantly better than the naïve prediction. We therefore combine these two using a neural network. FRAGFOLD-IDP enables better insight into backbone dynamics in IDPs and opens exciting possibilities for the design of disordered ensembles, disorder-to-order transitions, or design for protein dynamics. |
|---|