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 ρ.

Torque generation mechanism in F motor of ATP synthase elucidated by free-energy and Coulomb-energy landscapes along the c-ring rotation.

F portion of ATP synthase is a proton-motive rotary motor. The Coulombic attraction between the conserved acidic residues in the c-ring and the arginine in the a-subunit (aR) was early proposed to drive the c-ring rotation relative to the a-subunit, and has been actually observed in our previous molecular dynamics simulation with full atomistic description of F embedded in the membrane. In this study, to quantify the driving force, we conducted the umbrella sampling (US) and obtained the free-energy landscape for the c-ring rotation.

Coulombic Organization in Membrane-Embedded Rotary Motor of ATP Synthase.

The electrochemical potential difference of protons across the membrane is used to synthesize ATP through the proton-motive rotatory motion of the membrane-embedded region of ATP synthase called F. In this study, we illuminate the unsolved proton-motive rotary mechanism of F on the basis of atomistic simulation with full description of protein, lipid, and water molecules, and highlight the underlying Coulombic design. We first show that a water channel is spontaneously formed at the interfacial region between the rotor (-ring) and the stator (-subunit).

Over-Destabilization of Protein-Protein Interaction in Generalized Born Model and Utility of Energy Density Integration Cutoff.

The generalize Born (GB) model is frequently used in MD simulations of biomolecular systems in aqueous solution. The GB model is usually based on the so-called Coulomb field approximation (CFA) for the energy density integration. In this study, we report that the GB model with CFA overdestabilizes the long-range electrostatic attraction between oppositely charged molecules (ionic bond forming two-helix system and kinesin-tubulin system) when the energy density integration cutoff, r, which is used to calculate the Born energy, is set to a large value.