Details

Autor(en) / Beteiligte

• Christensen, Anders S
• Linnet, Troels E
• Borg, Mikael
• Boomsma, Wouter
• Lindorff-Larsen, Kresten
• Hamelryck, Thomas
• Jensen, Jan H
• Salsbury, Freddie

Titel

Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics

Ist Teil von

• PloS one, 2013-12, Vol.8 (12), p.e84123-e84123

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts--sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond ((h3)J(NC')) spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.