ProCS15: a DFT-based chemical shift predictor for backbone and Cβ atoms in proteins

Anders S Larsen; Lars A Bratholm; Anders S Christensen; Maher Channir; Jan H Jensen

doi:10.7717/peerj.1344

ProCS15: a DFT-based chemical shift predictor for backbone and Cβ atoms in proteins

PeerJ. 2015 Oct 20:3:e1344. doi: 10.7717/peerj.1344. eCollection 2015.

Authors

Anders S Larsen¹, Lars A Bratholm², Anders S Christensen³, Maher Channir², Jan H Jensen²

Affiliations

¹ Department of Pharmacy, University of Copenhagen , Copenhagen , Denmark.
² Department of Chemistry, University of Copenhagen , Copenhagen , Denmark.
³ Department of Chemistry, University of Wisconsin-Madison , Madison, WI , USA.

Abstract

We present ProCS15: a program that computes the isotropic chemical shielding values of backbone and Cβ atoms given a protein structure in less than a second. ProCS15 is based on around 2.35 million OPBE/6-31G(d,p)//PM6 calculations on tripeptides and small structural models of hydrogen-bonding. The ProCS15-predicted chemical shielding values are compared to experimentally measured chemical shifts for Ubiquitin and the third IgG-binding domain of Protein G through linear regression and yield RMSD values of up to 2.2, 0.7, and 4.8 ppm for carbon, hydrogen, and nitrogen atoms. These RMSD values are very similar to corresponding RMSD values computed using OPBE/6-31G(d,p) for the entire structure for each proteins. These maximum RMSD values can be reduced by using NMR-derived structural ensembles of Ubiquitin. For example, for the largest ensemble the largest RMSD values are 1.7, 0.5, and 3.5 ppm for carbon, hydrogen, and nitrogen. The corresponding RMSD values predicted by several empirical chemical shift predictors range between 0.7-1.1, 0.2-0.4, and 1.8-2.8 ppm for carbon, hydrogen, and nitrogen atoms, respectively.

Keywords: Chemical shifts; NMR; Protein structure; Quantum chemistry.

Grants and funding

This work was supported by the Lundbeck Foundation and the Danish e-Infrastructure Cooporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.