Protein-ligand recognition using spherical harmonic molecular surfaces: towards a fast and efficient filter for large...

Area of Science:

• Computational chemistry and structural biology
• Molecular modeling and drug design

Background:

• Surface-shape complementarity is crucial for protein-ligand interactions and molecular docking.
• Previous methods utilized triangulated surface-meshes for molecular surface representation.

Purpose of the Study:

• To extend molecular surface approximation to spherical harmonic surfaces.
• To enable efficient checking of surface-shape complementarity between ligands and receptor cavities.
• To develop a novel docking procedure and virtual screening tool.

Main Methods:

• Approximation of molecular surfaces (ligands and receptor cavities) using spherical harmonic expansions.
• Identification of surface features (lobes and holes) via contour maps of radius functions.
• Superposition of surfaces by minimizing the distance between spherical harmonic expansion coefficients.

Main Results:

• Demonstrated docking procedure capabilities on 35 known protein-ligand crystal structures.
• Successfully applied the method as a filter for virtual screening of conformational sampling.
• Validated virtual screening on the platelet thrombin receptor.

Conclusions:

• Spherical harmonic surfaces provide an effective means to approximate molecular surfaces for complementarity assessment.
• The developed method offers an efficient approach for molecular docking and virtual screening.
• This technique can significantly aid in identifying potential drug candidates and optimizing docking studies.