Rapid calculation of protein chemical shifts using bond polarization theory and its application to protein structure refinement

Abstract

Although difficult to analyze, NMR chemical shifts provide detailed information on protein structure. We have adapted the semi-empirical bond polarization theory (BPT) to protein chemical shift calculation and chemical shift driven protein structure refinement. A new parameterization for BPT amide nitrogen chemical shift calculation has been derived from MP2 ab initio calculations and successfully evaluated using crystalline tripeptides. We computed the chemical shifts of the small globular protein ubiquitin, demonstrating that BPT calculations can match the results obtained at the DFT level of theory at very low computational cost. In addition to the calculation of chemical shift tensors, BPT allows the calculation of chemical shift gradients and consequently chemical shift driven geometry optimizations. We applied chemical shift driven protein structure refinement to the conformational analysis of a set of Trypanosoma brucei (the causative agent of African sleeping sickness) tryparedoxin peroxidase Px III structures. We found that the interaction of Px III with its reaction partner Tpx seems to be governed by conformational selection rather than by induced fit.

1H line width dependence on MAS speed in solid state NMR – Comparison of experiment and simulation

“…level crossing during MAS) [51]. All nuclear shielding tensors were calculated using the bond polarization theory [52][53][54] (BPT). Due to the zwitterionic character of the crystal molecules within the unit cell, wide-ranging polarization effects had to be considered by taking periodic boundary conditions into account.…”

Configuration determination by residual dipolar couplings: accessing the full conformational space by molecular dynamics with tensorial constraints

“…RCSAs have been measured successfully using a variety of methods, [108][109][110] and they should result in particularly valuable restraints in protonless spin systems as long as the corresponding CSA tensors can be estimated. 111,112 We are currently working on the corresponding extensions of the COSMOS program. The aim for the future is therefore the inclusion of as many constraints to the MDOC approach as possible.…”

Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

“…The BPT (Bond Polarization Theory) is the starting point for the calculation of atomic charges, describing the dependence of expectation values from polarization [76]. The definition of a local charge operator̂(site ) is a prerequisite to calculate atomic charges :…”