The implicit solvent framework which treats solvent as a continuum can offer much greater effective simulation speeds compared to the explicit solvent models. Yet existing practical implicit solvation models - the generalized Born (GB) or Poisson-Boltzmann (PB) - are no longer accurate enough for the increased demands of the community in most areas. The accuracy limitations of these models are direct consequences of many approximations made, such as the neglect of solvent response beyond the dipole. In particular, the dipole level linear response electrostatics misses the effect of charge hydration asymmetry related to quadrupole and octupole level responses of water at the surface of charged or polar solutes. We propose a new computationally efficient way of adding these critical solvation effects to the basic continuum solvent models widely used. The missing physics is introduced into the continuum electrostatics via simultaneous, systematic electric multipoles and finite-size corrections to the PB and GB models utilizing analytical electrostatics framework (ALPB) developed earlier. Our approach combines most of the accuracy of the explicit solvent representation with the effectiveness of the PB/GB formalism. The new PB-based model reproduces the TIP3P hydration free energies of 22 dipeptides with RMSE better than 1 kcal/mol.

Building accurate and fast implicit solvation models

2019 Fall National Meeting

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