ProToss

Overview

Protoss is a fully automated hydrogen prediction tool for protein-ligand complexes. It adds missing hydrogen atoms to protein structures (PDB-format) and detects reasonable protonation states, tautomers, and hydrogen coordinates of both protein and ligand molecules.

Method

Protoss identifies missing hydrogen atoms in a protein-ligand complex by a detection of free valences of all heavy atoms. Existence and coordinates of polar hydrogens are determined on the basis of the following degrees of freedom:

• rotatable hydrogens in terminal groups (e.g. hydroxyls and amines)
• tautomers and protonation states of arbitrary chemical moieties (including ligand molecules)
• flips of ambiguous amino acid side-chain 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 overlapping entries which might be annotated in the original protein structure are removed, as they could disturb the analysis of molecular interactions.

Software / Webservice

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

People and References

[1] Lippert, T., Rarey, M.: Fast automated placement of polar hydrogen atoms in protein-ligand complexes. Journal of Cheminformatics 2009, 1:13

[2] Bietz, S., Urbaczek, S., Schulz, B., Rarey, M.: Protoss: a holistic approach to predict tautomers and protonation states in protein-ligand complexes. Journal of Cheminformatics 2014, 6:12.