DIELECTRIC CONTINUUM MODELING FOR THE DE NOVO DESIGNED CALCIUM CHANNEL CALC6.3: STRUCTURE PREPARATION, MESHGENERATION, AND CALCIUM SELECTIVITY

Abstract

This paper presents an integrated software package for continuum dielectric studies of the de novo designed calcium channel CalC6.3. The package combines Python scripts for cleaning and repairing the original PDB structure (PDB ID: 9DZW) with PDB2PQR to generate a corre-sponding PQR file containing atomic coordinates, partial charges, and radii. It incorporates the Gaussian Ion Channel Molecular Surface Generation package to construct high-quality triangular molecular surface meshes that preserve the complex channel pore geometry while maintaining suffi-nterface-fitted tetrahedral meshes of a simulation box consisting of protein, membrane, and solvent regions. The integrated software package further integrates the structure-preparation and mesh- size-nite element solver to compute electrostatic potentials and ionic concentrations, streamlining the complete workflow from structure preparation to numerical solution. Numerical experiments for an ionic solution containing Ca2+, Na+ , and Cl-ions show preferential Ca2+ accumulation in the narrow selectivity filter formed by six Glu residues, supporting the experimentally observed calcium selectivity of CalC6.3. They also suggest that a smoother molecular surface mesh can improve the convergence and performance of the finite element solver.