Recent progress in adapting Poisson–Boltzmann methods to molecular simulations

Electrostatic solvation modeling based upon the Poisson–Boltzmann equation is widely used in studies of biomolecular structures and functions. This manuscript provides a thorough review of published efforts to adapt the numerical Poisson–Boltzmann methods to molecular simulations so that these methods can be extended to biomolecular studies involving conformational fluctuation and/or dynamics. We first review the fundamental works on how to define the electrostatic free energy and the Maxwell stress tensor. These topics are followed by three different strategies in developing algorithms to compute electrostatic forces and how to improve their numerical performance. Finally procedures are also presented in detail on how to discretize these algorithms for numerical calculations. Given the pioneer works reviewed here, further developmental efforts will be on how to balance efficiency and accuracy in these theoretical sound approaches — two important issues in applying any numerical algorithms for routine biomolecular applications. Even if not reviewed here, more advanced numerical solvers are certainly necessary to achieve higher accuracy than the widely used classical methods to improve the overall performance of the numerical Poisson–Boltzmann methods.