Protein Structure Refinement using Quantum Mechanics-Based Chemical Shift Prediction

Abstract

Alternative title: Small changes in protein structure improves quantum mechanics-based chemical shift prediction

Can QM-based chemical shift prediction be made as accurate as empirical methods by making small changes to the protein structure?

If these changes are small enough, it may not make sense to talk if an improvement

Real question (not addressed here) if protein structure determination is more accurate with ProCS15. E.g. does one get better structures starting from 4-6 Å structures?

Comparison to CHARMM only refinement?

Introduction

Some of us recently showed (Christensen 2013) that protein refinement using a DFT-based backbone amide proton chemical shift predictor (ProCS) yielded more accurate hydrogen-bond geometries and \(^\text{3h}\)J\(_\text{NC'}\) coupling constants involving backbone amide groups than corresponding refinement with CamShift. Furthermore, the ProCS predictions based on the structurally refined ensemble yielded amide proton chemical shift predictions that were at least as accurate as CamShift. This suggests that the larger RMSD observed for QM-based chemical shift predictions may, at least in part, be due to relatively small errors in the protein structures used for the predictions, and not a deficiency in the underlying method. This paper tests whether this is true for other back bone atoms and C\(\beta\) using ProCS15 (Larsen 2015). We first describe how the isotropic chemical shielding values can be related to the experimental chemical shifts as part of the simulation. Secondly, we perform Monte Carlo simulations to refine the structures of xx proteins ...