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Updated: Jul 6, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
Structure prediction of domain insertion proteins from structures of individual domains
Monica Berrondo1, Marc Ostermeier, Jeffrey J Gray
1Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Abstract:
Multidomain proteins continue to be a major challenge in protein structure prediction. Here we present a Monte Carlo (MC) algorithm, implemented within Rosetta, to predict the structure of proteins in which one domain is inserted into another. Three MC moves combine rigid-body and loop movements to search the constrained conformation by structure disruption and subsequent repair of chain breaks. Local searches find that the algorithm samples and recovers near-native structures consistently. Further global searches produced top-ranked structures within 5 A in 31 of 50 cases in low-resolution mode, and refinement of top-ranked low-resolution structures produced models within 2 A in 21 of 50 cases. Rigid-body orientations were often correctly recovered despite errors in linker conformation. The algorithm is broadly applicable to de novo structure prediction of both naturally occurring and engineered domain insertion proteins.
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