pPerturb

pPerturb predicts long-distance energetic couplings and mutation-induced stability changes within proteins to quantify intraprotein interaction network strength and characterize allosteric signal propagation for residues up to approximately 12-15 Å.

Key Features:

• Long-distance coupling prediction: Predicts energetic couplings between residues separated by up to approximately 12-15 Å.
• Mutation-induced stability changes: Estimates stability changes caused by single-point mutations and their destabilization effects.
• Intraprotein interaction quantification: Rapidly quantifies the strength of intraprotein interaction networks in experimentally relevant units.
• First-shell and second-shell interactions: Accounts for both first-shell (direct neighbors) and second-shell interactions in analyses.
• Residue-specific outputs: Provides residue-specific predictions of coupling distances and overall perturbation magnitudes.
• Validation: Methodology is experimentally validated against a dataset of 375 mutations across 19 proteins.
• Local stability and packing analysis: Predicts local stabilities, side chain orientation or packing changes upon ligand binding, and impacts on buried residues.
• Allosteric insights: Offers measures relevant to allosteric signal propagation characteristics and the distribution of energetic couplings.

Scientific Applications:

• Allosteric pathway analysis: Characterizes propagation of allosteric signals through distributions of energetic couplings.
• Mutational effect assessment: Evaluates destabilization effects and stability changes induced by mutations.
• Residue-level stability mapping: Maps local stabilities and identifies residues with altered packing or side chain orientations after ligand binding.
• Buried residue impact assessment: Assesses the impact of mutations on buried residues and their contribution to overall protein stability.

Methodology:

An experimentally validated perturbation approach is applied and validated against a dataset of 375 mutations across 19 proteins.