Prediction of protein backbone torsion angles from NMR chemical shifts.
TALOS+ is a hybrid system for empirical prediction of protein phi and psi backbone torsion angles using a combination of six kinds (HN, HA, CA, CB, CO, N) of chemical shift assignments for a given residue sequence.
TALOS+ is an enhanced version of the earlier TALOS system which improves upon the original TALOS database mining approach by including a neural network classification scheme, as well as a larger database of 200 proteins. This improved approach allows TALOS+ to make a larger number of useful backbone angle predictions, 88% of residues in a given protein on average.
The original TALOS approach is an extension of the well-known observation that many kinds of secondary chemical shifts (i.e. differences between chemical shifts and their corresponding random coil values) are highly correlated with aspects of protein secondary structure. The goal of TALOS+ is to use secondary shift and sequence information in order to make quantitative predictions for the protein backbone angles phi and psi, and to provide a measure of the uncertainties in these predictions. In the original TALOS approach, we search a high-resolution structural database for the 10 best matches to the secondary chemical shifts of given residue in a target protein along with its two flanking neighbors (a residue triplet). If there is a consensus of phi and psi angles among the 10 best database matches, then we use these database triplet structures to form a prediction for the backbone angles of the target residue.
The TALOS+ approach adds an artificial neural network (ANN) classification scheme to this database mining approach. The neural network analyzes the chemical shifts and sequence to estimate the likelihood of a given residue being in a sheet, helix, or loop conformation. This ANN classification information is combined with the database mining results to increase the number of residues where useful backbone angle predictions can be made.
In addition, TALOS+ also offers several new features compared to the original TALOS program:
- In order to expand the program's ability to predict backbone torsion angles, TALOS+ now also considers the frequently encountered cases where residue assignments are lacking. Although the fraction of such residues for which unambiguous predictions can be made tends to be significantly lower, the reliability of such predictions remains high.
- For convenience, and in order to prevent assignment of backbone torsion angles to regions that are dynamically disordered, TALOS+ also reports an estimated backbone order parameter S2 derived from the chemical shifts in a way recently described by Berjanskii and Wishart (J. Am. Chem. Soc. 127: 14970-14971).
- TALOS+ also provides ANN-predicted secondary structure information from the chemical shifts, with about 89% prediction accuracy.
|NMRbox Version||Software Version|