The Intrinsic Radius as a Key Parameter in the Generalized Born Model to Adjust Protein-Protein Electrostatic Interaction

The generalized Born (GB) model is an extension of the continuum dielectric theory of Born solvation energy and is a powerful method for accelerating the molecular dynamic (MD) simulations of charged biological molecules in water. While the effective dielectric constant of water that varies as a function of the separation distance between solute molecules is incorporated into the GB model, adjustment of the parameters is indispensable for accurate calculation of the Coulomb (electrostatic) energy. One of the key parameters is the lower limit of the spatial integral of the energy density of the electric field around a charged atom, known as the intrinsic radius rho. Although ad hoc adjustment of rho has been conducted to improve the Coulombic (ionic) bond stability, the physical mechanism by which rho affects the Coulomb energy remains unclear. Via energetic analysis of three differently sized systems, here, we clarify that the Coulomb bond stability increases with increasing rho and that the increased stability is caused by the interaction energy term, not by the self-energy (desolvation energy) term, as was supposed previously. Our results suggest that the use of larger values for the intrinsic radii of hydrogen and oxygen atoms, together with the use of a relatively small value for the spatial integration cutoff in the GB model, can better reproduce the Coulombic attraction between protein molecules.

Automated summary

The generalized Born (GB) model is a powerful method for accelerating MD simulations of charged biological molecules in water, and the adjustment of parameters is essential for accurate calculation of the Coulomb energy. This study clarifies that increasing the intrinsic radius rho in the GB model enhances the Coulomb bond stability through the interaction energy term. The use of larger values for the intrinsic radii of hydrogen and oxygen atoms, together with a relatively small value for the spatial integration cutoff, can better reproduce the Coulombic attraction between protein molecules.