Protein Structure Determination from Pseudocontact Shifts Using ROSETTA

By Christophe Schmitz, Robert M. Vernon, G. Otting, David Baker, Thomas Huber. 2012

115 citations recorded by the source corpus.

Paramagnetic metal ions generate pseudocontact shifts (PCSs) in nuclear magnetic resonance spectra that are manifested as easily measurable changes in chemical shifts. Metals can be incorporated into proteins through metal binding tags, and PCS data constitute powerful long-range restraints on the positions of nuclear spins relative to the coordinate system of the magnetic susceptibility anisotropy tensor (Δχ-tensor) of the metal ion. We show that three-dimensional structures of proteins can reliably be determined using PCS data from a single metal binding site combined with backbone chemical shifts. The program PCS-ROSETTA automatically determines the Δχ-tensor and metal position from the PCS data during the structure calculations, without any prior knowledge of the protein structure. The program can determine structures accurately for proteins of up to 150 residues, offering a powerful new approach to protein structure determination that relies exclusively on readily measurable backbone chemical shifts and easily discriminates between correctly and incorrectly folded conformations.

Subfields: Materials Chemistry, Molecular Biology

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Citations in the corpus

One contact for every twelve residues allows robust and accurate topology-level protein structure modeling (2013, neutral): “1–3 Recent advances in molecular modeling using experimental data such as NMR chemical shifts4–7 and sparse restraints,8–13 electron density from diffraction data,14 and cryoEM15,16 have shown that even very sparse information can significantly improve modeling.”
Pseudocontact Shift-Driven Iterative Resampling for 3D Structure Determinations of Large Proteins. (2016, methodology): “We have shown previously that the Rosetta fragment assembly method can be combined with PCSs to yield reliable 3D structure determinations of proteins with less than 150 residues, using PCSs generated from a single metal center [20].”
Integrative protein modeling in RosettaNMR from sparse paramagnetic restraints (2019, methodology): “This concept has then been extended with CS-Rosetta for the structure determination of larger proteins from backbone-only CSs and RDCs (Raman et al., 2010; Shen et al., 2008).”
Three-dimensional protein fold determination from backbone amide pseudocontact shifts generated by lanthanide tags at multiple sites. (2013, methodology): “GPS-Rosetta is an extended version of PCS-Rosetta (Schmitz et al., 2012), which uses experimental sets of PCSs from multiple metal binding sites for”
Chemical shift-based methods in NMR structure determination (2018, methodology): “PCS-Rosetta extends from Rosetta’s ab initio algorithm and makes use of chemical shift derived fragments together with a low-resolution energy function adjusted according to the PCS score (computed using experimental PCS data) [232].”
CS-ROSETTA (2018, methodology): “The presence of paramagnetic metal ions in proteins induce significant changes in chemical shift values resulting in long-range structural restraints known as PCS (Schmitz, Vernon, Otting, Baker, & Huber, 2012).”