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


ABSTRACT: 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.

SUBMITTER: Christensen AS 

PROVIDER: S-EPMC3877219 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Christensen Anders S AS   Linnet Troels E TE   Borg Mikael M   Boomsma Wouter W   Lindorff-Larsen Kresten K   Hamelryck Thomas T   Jensen Jan H JH  

PloS one 20131231 12


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 ref  ...[more]

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