Combining Rosetta with molecular dynamics (MD): A benchmark of the MD-based ensemble protein design.
J Struct Biol
; 203(1): 54-61, 2018 07.
Article
in En
| MEDLINE
| ID: mdl-29454111
ABSTRACT
Computational protein design is a set of procedures for computing amino acid sequences that will fold into a specified structure. Rosetta Design, a commonly used software for protein design, allows for the effective identification of sequences compatible with a given backbone structure, while molecular dynamics (MD) simulations can thoroughly sample near-native conformations. We benchmarked a procedure in which Rosetta design is started on MD-derived structural ensembles and showed that such a combined approach generates 20-30% more diverse sequences than currently available methods with only a slight increase in computation time. Importantly, the increase in diversity is achieved without a loss in the quality of the designed sequences assessed by their resemblance to natural sequences. We demonstrate that the MD-based procedure is also applicable to de novo design tasks started from backbone structures without any sequence information. In addition, we implemented a protocol that can be used to assess the stability of designed models and to select the best candidates for experimental validation. In sum our results demonstrate that the MD ensemble-based flexible backbone design can be a viable method for protein design, especially for tasks that require a large pool of diverse sequences.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Software
/
Protein Engineering
/
Molecular Dynamics Simulation
Language:
En
Journal:
J Struct Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2018
Type:
Article
Affiliation country:
Poland