H++

H++ predicts protonation states and prepares atomistic biomolecular structures (proteins, nucleic acids, and ligands) for molecular modeling and simulation.

Key Features:

• Protonation State Prediction: Calculates pK values of ionizable groups from atomic-resolution PDB structures using a continuum electrostatics model and allows specification of pH to determine equilibrium protonation states.
• Structure Completion: Adds missing hydrogen atoms and corrects side-chain conformations for residues such as HIS, GLN, and ASN.
• Format Compatibility: Outputs completed structures in PDB, PQR (PDB with charges and radii), and AMBER formats including inpcrd and prmtop.
• Error Checking and Correction: Performs extensive error and consistency checks on input structures and proposes corrections.
• Nucleic Acids and Ligands: Processes nucleic acid structures and includes ligands within the prepared models.
• Solvent and Ions: Generates a solvent box and adds specified common ions to facilitate explicit solvent molecular dynamics (MD) simulations.

Scientific Applications:

• Molecular Dynamics Preparation: Prepares atomistic systems with appropriate protonation, hydrogens, charges, and topology files for MD simulations.
• Electrostatics and pKa Analysis: Enables calculation of pK values and analysis of electrostatic properties of macromolecules under varying pH conditions.
• Enzyme Mechanism and Activity Studies: Supports studies of enzyme active sites by providing pH-dependent protonation states and corrected atomistic structures.
• Ligand Binding and Drug Design: Facilitates assessment of ligand protonation and binding interactions through prepared complexes and compatible AMBER files.
• Protein Stability and Structural Analysis: Aids evaluation of protein stability and side-chain conformations by supplying completed and validated atomistic models.

Methodology:

Computes pK values using a continuum electrostatics model on atomic-resolution PDB input, allows specification of pH, adds missing hydrogens, corrects HIS/GLN/ASN side-chain conformations, performs error and consistency checks, outputs PDB/PQR/inpcrd/prmtop files, and can generate a solvent box with specified ions.