PHEPS

PHEPS predicts pH-dependent electrostatic properties of globular proteins to evaluate atomic-level charge-dependent phenomena.

Key Features:

• Semi-Empirical Mean-Field Scheme: Employs a semi-empirical mean field scheme to evaluate global and local electrostatic properties as functions of pH.
• Electrostatic Parameters Assessed: Calculates protein proton binding, ionic site proton population, free energy electrostatic terms, proton affinities pK(a,i) of ionic groups and their Coulomb interactions with the entire charge multipole, molecular electrostatic potential at fixed pH, and local electrostatic potentials at specified points.
• Distance-Dependent Interaction Model: Implements a three-exponential empirical function for distance-dependent pair charge interactions that captures charge-charge, charge-dipole, and dipole-dipole contributions for fast calculations.
• Charge Customization Capabilities: Supports inclusion of non-polypeptide charges, additional ionizable groups with specified intrinsic pK(a)s, and fixed ions.
• Input Coordinates: Operates on atomic coordinates derived from PDB entries (PDB ID) or coordinate files.

Scientific Applications:

• pH-dependent electrostatics prediction: Predicts how pH changes affect protein electrostatics and protonation states.
• Structure–function correlation: Explains measured physicochemical characteristics by linking electrostatic calculations to protein atomic structures.
• Experimental design and analysis support: Assists planning and interpretation of experiments related to protein charge properties and charge-dependent phenomena.

Methodology:

PHEPS uses a semi-empirical mean-field approach with a three-exponential empirical function to compute distance-dependent pair charge interactions (charge-charge, charge-dipole, dipole-dipole) and derives proton affinities pK(a,i), ionic site proton populations, free energy electrostatic terms, and molecular and local electrostatic potentials from atomic coordinates (PDB ID or coordinate file), with options to include non-polypeptide charges, extra ionizable groups with intrinsic pK(a)s, and fixed ions.