Loeffler, Patrick and Schmitz, Samuel and Hupfeld, Enrico and Sterner, Reinhard and Merkl, Rainer (2017) Rosetta: MSF: a modular framework for multi-state computational protein design. PLOS COMPUTATIONAL BIOLOGY, 13 (6): e1005600. ISSN 1553-734X, 1553-7358
Full text not available from this repository. (Request a copy)Abstract
Computational protein design (CPD) is a powerful technique to engineer existing proteins or to design novel ones that display desired properties. Rosetta is a software suite including algorithms for computational modeling and analysis of protein structures and offers many elaborate protocols created to solve highly specific tasks of protein engineering. Most of Rosetta's protocols optimize sequences based on a single conformation (i.e. design state). However, challenging CPD objectives like multi-specificity design or the concurrent consideration of positive and negative design goals demand the simultaneous assessment of multiple states. This is why we have developed the multi-state framework MSF that facilitates the implementation of Rosetta's single-state protocols in a multi-state environment and made available two frequently used protocols. Utilizing MSF, we demonstrated for one of these protocols that multi-state design yields a 15% higher performance than single-state design on a ligand-binding benchmark consisting of structural conformations. With this protocol, we designed de novo nine retro-aldolases on a conformational ensemble deduced from a (beta alpha)(8)-barrel protein. All variants displayed measurable catalytic activity, testifying to a high success rate for this concept of multi-state enzyme design.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DE-NOVO DESIGN; INTERACTION SPECIFICITY; ENERGY FUNCTIONS; BINDING PROTEIN; STABILITY; SEQUENCE; OPTIMIZATION; ENSEMBLES; REDESIGN; ENZYMES; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 26 Feb 2019 10:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/751 |
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