Structure prediction of domain insertion proteins from structures of individual domains.
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.
Berrondo
Monica
M
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
Ostermeier
Marc
M
Gray
Jeffrey J
JJ
D000465:Algorithms; D008958:Models, Molecular; D009010:Monte Carlo Method; D017434:Protein Structure, Tertiary