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Prediction of protein structure with the coarse‐grained UNRES force field assisted by small X‐ray scattering data and knowledge‐based information
Author(s) -
Karczyńska Agnieszka S.,
Mozolewska Magdalena A.,
Krupa Paweł,
Giełdoń Artur,
Liwo Adam,
Czaplewski Cezary
Publication year - 2018
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25421
Subject(s) - small angle x ray scattering , scattering , force field (fiction) , molecular dynamics , replica , materials science , field (mathematics) , crystallography , computer science , physics , chemistry , optics , mathematics , computational chemistry , artificial intelligence , art , visual arts , pure mathematics
A new approach to assisted protein–structure prediction has been proposed, which is based on running multiplexed replica exchange molecular dynamics simulations with the coarse‐grained UNRES force field with restraints derived from knowledge‐based models and distance distribution from small angle X‐ray scattering (SAXS) measurements. The latter restraints are incorporated into the target function as a maximum‐likelihood term that guides the shape of the simulated structures towards that defined by SAXS. The approach was first verified with the 1KOY protein, for which the distance distribution was calculated from the experimental structure, and subsequently used to predict the structures of 11 data‐assisted targets in the CASP12 experiment. Major improvement of the GDT_TS was obtained for 2 targets, minor improvement for other 2 while, for 6 target GDT_TS deteriorated compared with that calculated for predictions without the SAXS data, partly because of assuming a wrong multimeric state (for Ts866) or because the crystal conformation was more compact than the solution conformation (for Ts942). Particularly good results were obtained for Ts909, in which use of SAXS data resulted in the selection of a correctly packed trimer and, subsequently, increased the GDT_TS of monomer prediction. It was found that running simulations with correct oligomeric state is essential for the success in SAXS‐data‐assisted prediction.