Protoss

Overview

Protoss is a fully automated hydrogen atom placement tool for protein-ligand complexes. It adds missing hydrogen atoms to protein structures and detects reasonable protonation states, tautomeric states, and hydrogen coordinates of both protein and ligand molecules by optimizing the hydrogen bond network.

Method

Protoss identifies missing hydrogen atoms in a protein-ligand complex by detecting the free valences of all heavy atoms. The existence and coordinates of polar hydrogens are determined considering the following degrees of freedom:

• rotatable hydrogens in terminal groups (e.g., hydroxy and amine groups)
• tautomeric and protonation states of chemical moieties (including ligand molecules)
• flips of ambiguous residue sidechain orientations (Asn, Gln, and His)
• alternative orientations of water molecules

Protoss investigates hydrogen bonds, metal interactions, and repulsive atom contacts for all possible states and calculates an optimal hydrogen bonding network within these degrees of freedom. Furthermore, alternative conformations or clashing atoms in the original structure are removed as they could hamper the analysis of molecular interactions.

Software Availability

We are offering Protoss as part of our ProteinsPlus web service. Please visit https://proteins.plus, upload your protein, and choose Protoss.

References

Bietz, S.; Urbaczek, S.; Schulz, B.; Rarey, M. Protoss: A Holistic Approach to Predict Tautomers and Protonation States in Protein-Ligand Complexes. J Cheminform 2014, 6, 12. DOI: https://doi.org/10.1186/1758-2946-6-12
Lippert, T.; Rarey, M. Fast Automated Placement of Polar Hydrogen Atoms in Protein-Ligand Complexes. J Cheminform 2009, 1 (1), 13. DOI: https://doi.org/10.1186/1758-2946-1-13