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

Area of Science:

• Computational Chemistry
• Structural Biology
• Nuclear Magnetic Resonance (NMR) Spectroscopy

Background:

• Accurate prediction of chemical shifts is crucial for protein structure determination and analysis using NMR.
• Existing computational methods for chemical shift prediction can be computationally intensive.
• Isotropic chemical shielding is a key parameter in NMR spectroscopy.

Purpose of the Study:

• To develop a fast and accurate program, ProCS15, for calculating isotropic chemical shielding values.
• To evaluate the performance of ProCS15 against experimental chemical shift data.
• To compare ProCS15's performance with other computational approaches.

Main Methods:

• ProCS15 utilizes approximately 2.35 million OPBE/6-31G(d,p)//PM6 calculations on tripeptides and hydrogen-bonding models.
• The program computes chemical shielding for backbone and Cβ atoms.
• Performance is assessed by comparing predicted values to experimental chemical shifts in Ubiquitin and Protein G using linear regression.

Main Results:

• ProCS15 predicts chemical shielding values with RMSD values up to 2.2 ppm (carbon), 0.7 ppm (hydrogen), and 4.8 ppm (nitrogen) for Ubiquitin and Protein G.
• These results are comparable to those obtained using full structure calculations with OPBE/6-31G(d,p).
• Utilizing NMR-derived structural ensembles further reduced maximum RMSD values to 1.7 ppm (carbon), 0.5 ppm (hydrogen), and 3.5 ppm (nitrogen).

Conclusions:

• ProCS15 offers a rapid and accurate method for calculating protein chemical shielding values.
• The program's performance is competitive with established, more computationally demanding methods.
• ProCS15 has the potential to accelerate NMR-based protein structure analysis and research.