SPACE

SPACE predicts and analyzes biomolecular structures and interactions by leveraging surface complementarity, interatomic contacts, and environmental interactions.

Key Features:

• Surface Complementarity: Utilizes contact surface area and atomic chemical properties to predict amino acid side-chain conformations on a fixed protein backbone with a scoring function incorporating van der Waals forces and solvation free energy optimized for partially buried side chains.
• Iterative and Stochastic Searching: Employs iterative and stochastic algorithms to predict chi1 angles, reporting 92–93% correct predictions for buried residues, 82–84% for all residues, and an approximate 1.7 Å RMSD for side-chain heavy atoms.
• Ligand-Protein Interaction Analysis (LPC): Calculates solvent-accessible surfaces, identifies contacting residues and interaction types including potential hydrogen bonds, and predicts changes in binding strength following chemical modifications of ligands.
• Structural Unit Contacts (CSU): Analyzes contacts between structural units such as helices, sheets, strands, and residues to characterize protein-protein and intra-protein contacts.
• Molecular Docking: Performs docking by maximizing a complementarity function based on atomic contact surface area and chemical properties to predict ligand orientations and effects of atom substitutions.
• Mutation Analysis (MutaProt): Compares pairs of PDB files differing by one or two amino acids to analyze microenvironments, solvent accessibility, and contact information around exchanged residues.
• Crystal Environment Modeling (CryCo): Constructs and analyzes crystal environments and intermolecular contacts to characterize crystallographic packing.
• Protein Contact Maps (CMA): Constructs and analyzes protein contact maps to provide insights into residue-residue interactions and overall structural topology.
• Visualization Tools: Provides 3D structural representations using Chime or Java-based Jmol for presentation of analyses.

Scientific Applications:

• Side-chain conformation prediction: Predicts amino acid side-chain conformations on fixed backbones, including partially buried residues.
• Ligand–protein interaction analysis: Identifies contacting residues, hydrogen bonds, and solvent-accessible surfaces and predicts binding-strength changes after ligand modification.
• Mutation effect analysis: Assesses structural consequences of one- or two-residue substitutions by comparing PDB pairs and analyzing local microenvironments.
• Molecular docking and ligand design: Predicts ligand orientations and guides atom substitutions to design improved ligands based on surface complementarity.
• Crystallographic contact analysis: Constructs crystal environments and analyzes crystal contacts to support crystallography and packing studies.

Methodology:

Analyzes interatomic contacts and surface complementarity; treats ligands and proteins as rigid bodies with limited adjustments to residues lining binding sites; uses scoring functions incorporating van der Waals forces and solvation free energy and maximizes complementarity functions based on atomic contact surface area and chemical properties; employs iterative and stochastic searching for chi1 prediction; calculates solvent-accessible surfaces; constructs crystal environments and protein contact maps; compares PDB pairs for mutation microenvironment analysis.