HotPoint

HotPoint predicts protein–protein interface hot spots that significantly contribute to binding free energy using an empirical model.

Key Features:

• Empirical model: Integrates solvent occlusion and total knowledge-based residue pair potentials to identify hot spots at interfaces.
• Prediction performance: Reports an empirical accuracy of approximately 70% for hot spot identification.
• Input requirements: Operates on a provided protein complex with two chain identifiers that delineate the interface of interest.
• Hot spot predictions: Outputs residues predicted to be energetic hot spots contributing to binding free energy.
• Residue properties table: Provides a tabulated set of properties for each residue at the specified interface.
• 3D visualization output: Produces a three-dimensional representation of the protein complex with predicted hot spots highlighted.
• Result export: Allows export of results in text file format for downstream analysis.

Scientific Applications:

• Binding-site characterization: Identifies key energetic residues for analysis of protein–protein interaction interfaces.
• Small-molecule and therapeutic design: Guides rational design of small molecules and other agents that target protein–protein interactions by pinpointing critical residues.

Methodology:

Predictions are generated by an empirical model that applies rules based on solvent occlusion and total knowledge-based residue pair potentials to residues at interfaces defined by two chain identifiers within a protein complex.