MOLE

MOLE identifies and characterizes molecular channels, tunnels, and pores in biomolecular structures using Dijkstra's path search on a Voronoi mesh to support structural and functional analysis.

Key Features:

• Automated identification and characterization: Fully automated detection and characterization of channels, tunnels, and pores across diverse biomolecular systems including gramicidine, acetylcholinesterase, cytochromes P450, potassium channels, DNA quadruplexes, ribozymes, and the large ribosomal subunit.
• Advanced algorithmic approach: Uses Dijkstra's path search algorithm applied to a Voronoi mesh to map complex networks of channels precisely.
• Trajectory analysis: Enables analysis over numerous molecular dynamics trajectory snapshots to capture dynamic channel behavior.
• Versatility and robustness: Benchmark tests report superior speed, robustness, and versatility, and capability to handle large molecular structures and intricate channel networks.
• Physicochemical property estimation (MOLE 2.0): Estimates channel properties including hydropathy, hydrophobicity, polarity, charge, and mutability.
• Validation and biological relevance: Assessments of X-ray structures indicate that estimated physicochemical properties align with known channel functions, reflecting relevance to molecular recognition and enzyme substrate specificity.

Scientific Applications:

• Structural and functional analysis of channels: Investigation of molecular recognition and enzyme substrate specificity via identification and characterization of channels and pores.
• Drug design and enzymology: Hypothesis generation about channel function and guidance for ligand or inhibitor design based on channel geometry and physicochemical properties.
• Comparative analysis across biomolecules: Comparative mapping and characterization of channel networks in proteins and nucleic acid systems such as cytochromes P450, potassium channels, DNA quadruplexes, and the ribosome.
• Dynamics of channel behavior: Study of conformational changes and temporal properties of channels using analysis of molecular dynamics trajectory snapshots.

Methodology:

Applies Dijkstra's path search algorithm to a Voronoi mesh, performs analysis across molecular dynamics trajectory snapshots, and computes channel physicochemical properties (hydropathy, hydrophobicity, polarity, charge, mutability).