Protocols for Requirement-Driven Protein Design in the Rosetta Modeling Program.
J Chem Inf Model
; 58(5): 895-901, 2018 05 29.
Article
em En
| MEDLINE
| ID: mdl-29659276
ABSTRACT
We have developed a set of protocols in the molecular modeling program Rosetta for performing requirement-driven protein design. First, the user specifies a set of structural features that need to be present in the designed protein. These requirements can be general (e.g., "create a protein with five helices"), or they can be very specific and require the correct placement of a set of amino acids to bind a ligand. Next, a large set of protein models are generated that satisfy the design requirements. The models are built using a method that we recently introduced into Rosetta, called SEWING, that rapidly assembles novel protein backbones by combining pieces of naturally occurring proteins. In the last step of the process, rotamer-based sequence optimization and backbone refinement are performed with Rosetta, and a variety of quality metrics are used to pick sequences for experimental characterization. Here we describe the input files and user options needed to run SEWING and perform requirement-driven design and provide detailed instructions for two specific applications of the process the design of new structural elements at a protein-protein interface and the design of ligand binding sites.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Proteínas
/
Modelos Moleculares
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article