Mar 27, 2019

High Accuracy Protein Structures from Minimal Sparse Paramagnetic Solid-State NMR Restraints

Angewandte Chemie
Alberto PerezJustin L MacCallum

Abstract

There is a pressing need for new computational tools to integrate data from diverse experimental approaches in structural biology. We present a strategy that combines sparse paramagnetic solid-state NMR restraints with physics-based atomistic simulations. Our approach explicitly accounts for uncertainty in the interpretation of experimental data through the use of a semi-quantitative mapping between the data and the restraint energy that is calibrated by extensive simulations. We apply our approach to solid-state NMR data for the model protein GB1 labeled with Cu2+ -EDTA at six different sites. We are able to determine the structure to 0.9 Å accuracy within a single day of computation on a GPU cluster. We further show that in some cases, the data from only a single paramagnetic tag are sufficient for accurate folding.

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Mentioned in this Paper

Site
Structure
GABBR1
Simulation
Protein Folding
Cupric cation
Computed (Procedure)
Solid state

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