From Implicit to Explicit: An Interaction-Reorganization Approach to Molecular Solvation Energy

Accurate calculation of solvation energies has long fascinated
researchers, but complex interactions within bulk water molecules
pose significant challenges. Currently, molecular solvation energy
calculations are mostly based on implicit solvent approximations in
which the solvent molecules are treated as continuum dielectric media.
However, the implicit solvent approach is not ideal because it lacks
certain real solvation effects, such as that of the first solvation
shell, etc. Here, we propose an explicit solvent approach, interaction-reorganization
solvation (IRS) method, for molecular solvation energy calculations.
The IRS approach achieves predictive accuracy comparable to that of
the widely recognized solvation model based on the density (SMD) method
and is significantly more accurate than that of the Poisson–Boltzmann/generalized
Born surface area (PB/GBSA) methods. This is demonstrated in both
the correlation coefficient and the mean absolute error (MAE) with
respect to the experimental data. The IRS method is based on molecular
dynamics simulation in explicit solvent and does not need to solve
Poisson–Boltzmann or Schrödinger equations. On the other
hand, the accuracy of the IRS method does depend on the accuracy of
the molecular force field used in MD simulations. We expect that the
IRS method will be very useful for the solvation energy calculations
of molecules.

长期以来，溶剂化能（solvation energy）的精准计算始终是研究者们热切关注的研究方向，但体相水分子间的复杂相互作用却带来了诸多严峻挑战。当前，分子溶剂化能的计算大多采用隐式溶剂近似（implicit solvent approximations），即将溶剂分子视作连续介质电介质（continuum dielectric media）进行建模处理。然而，隐式溶剂方法并不理想，因其无法复现部分真实溶剂化效应，例如第一溶剂化层（first solvation shell）的作用等。在此，我们提出一种显式溶剂方法——相互作用重组溶剂化（interaction-reorganization solvation, IRS）法，用于分子溶剂化能的计算。该IRS方法的预测精度可与广受认可的基于密度的溶剂化模型（Solvation Model based on Density, SMD）相媲美，且显著优于泊松-玻尔兹曼/广义玻恩表面积（Poisson–Boltzmann/generalized Born surface area, PB/GBSA）方法。这一点可通过与实验数据对比得到的相关系数与平均绝对误差（Mean Absolute Error, MAE）得到验证。IRS方法基于显式溶剂环境下的分子动力学（Molecular Dynamics, MD）模拟，无需求解泊松-玻尔兹曼方程或薛定谔（Schrödinger）方程。另一方面，IRS方法的精度取决于分子动力学模拟中所采用的分子力场的精度。我们预期，IRS方法将在分子溶剂化能计算领域具备极高的应用价值。