Characterization of partially ordered states in the intrinsically disordered N-terminal domain of p53 using millisecond molecular dynamics simulations
The exploration of intrinsically disordered proteins in isolation is a crucial step to understand their complex dynamical behavior. In particular, the emergence of partially ordered states has not been explored in depth. The experimental characterization of such partially ordered states remains elus...
| Autores: | , , |
|---|---|
| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2020 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/45265 |
| Acesso em linha: | http://hdl.handle.net/10230/45265 http://dx.doi.org/10.1038/s41598-020-69322-2 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Intrinsically disordered proteins Peptides Proteins |
| Resumo: | The exploration of intrinsically disordered proteins in isolation is a crucial step to understand their complex dynamical behavior. In particular, the emergence of partially ordered states has not been explored in depth. The experimental characterization of such partially ordered states remains elusive due to their transient nature. Molecular dynamics mitigates this limitation thanks to its capability to explore biologically relevant timescales while retaining atomistic resolution. Here, millisecond unbiased molecular dynamics simulations were performed in the exemplar N-terminal region of p53. In combination with state-of-the-art Markov state models, simulations revealed the existence of several partially ordered states accounting for [Formula: see text] 40% of the equilibrium population. Some of the most relevant states feature helical conformations similar to the bound structure of p53 to Mdm2, as well as novel [Formula: see text]-sheet elements. This highlights the potential complexity underlying the energy surface of intrinsically disordered proteins. |
|---|