SphereCon

SphereCon estimates residue relative solvent accessible area (RSA) in proteins by computing geometric sphere–cone intersection volumes and by using inter-residue distance or contact matrices when atomic coordinates are limited.

Key Features:

• Estimation from limited data: Calculates the volume of intersection between a sphere and a cone with a cut-out directed away from the residue, considering surrounding atoms to estimate RSA from minimal structural information.
• Handling incomplete structures: Estimates the position and volume of residue atoms when atomic coordinates are unknown, unreliable, or missing.
• Correlation with direct RSA computation: Produces estimates that correlate almost perfectly with directly computed RSA values for reliable input structures.
• Performance against other methods: Outperforms other indirect RSA estimation methods and provides accurate results even when amino acid identities are unknown.
• Utilization of distance/contact matrices: Estimates RSA from inter-residue distance and contact matrices without requiring detailed atom coordinates.
• Input formats and options: Implemented as a Python script (spherecon.py) that processes PDB files or distance matrix files and supports selection of chain, specific residues, and inclusion of alpha carbons or backbone atoms.

Scientific Applications:

• Mutation impact prediction: Provides RSA values used to predict effects of mutations on protein function and pathogenicity.
• Protein stability and interaction analysis: Informs assessments of protein stability and protein–protein or protein–ligand interactions via solvent accessibility metrics.
• Structural analysis from sparse data: Enables RSA-based analyses in contexts where only inter-residue distance or contact matrices are available or structures are incomplete, supporting structural bioinformatics and computational studies relevant to drug design and disease modeling.

Methodology:

Computes the intersection volume of a sphere with a cone cut-out directed away from the residue to infer solvent accessibility, accepts PDB or distance/contact matrix inputs, and is implemented as the Python script spherecon.py with options to select chains, residues, and include alpha carbons or backbone atoms.