Derivation of Fixed Partial Charges for Amino Acids Accommodating a Specific Water Model and Implicit Polarization

We have developed the IPolQ method for fitting nonpolarizable
point
charges to implicitly represent the energy of polarization for systems
in pure water. The method involves iterative cycles of molecular dynamics
simulations to estimate the water charge density around the solute
of interest, followed by quantum mechanical calculations at the MP2/cc-pV­(T+d)­Z
level to determine updated solute charges. Lennard-Jones parameters
are updated starting from the Amber FF99SB nonbonded parameter set
to accommodate the new charge model, guided by the comparisons to
experimental hydration free energies (HFEs) of neutral amino acid
side chain analogs and assumptions about the computed HFEs for charged
side chains. These Lennard-Jones parameter adjustments for side-chain
analogs are assumed to be transferable to amino acids generally, and
new charges for all standard amino acids are then derived in the presence
of water modeled by TIP4P-Ew. Overall, the new charges depict substantially
more polarized amino acids, particularly in the backbone moieties,
than previous Amber charge sets. Efforts to complete a new force field
with appropriate torsion parameters for this charge model are underway.
The IPolQ method is general and applicable to arbitrary solutes.

我们开发了IPolQ方法，用于拟合非极化点电荷，以隐式表征纯水环境中体系的极化能。该方法包含迭代分子动力学模拟循环，以估算目标溶质周围的水分子电荷密度；随后以MP2/cc-pV(T+d)Z级别开展量子力学计算，从而更新溶质电荷参数。Lennard-Jones参数以Amber FF99SB非键相互作用参数集为基础进行更新，以适配新的电荷模型，更新过程参照中性氨基酸侧链类似物的实验水化自由能（hydration free energies, HFEs），并结合带电侧链水化自由能的计算假设进行引导。上述针对侧链类似物的Lennard-Jones参数调整被假设可推广至所有氨基酸，随后在以TIP4P-Ew模型表征的水环境中，推导得到所有标准氨基酸的全新电荷参数。总体而言，相较于此前的Amber电荷集，这套全新电荷能更显著地展现出氨基酸（尤其是骨架基团）的极化特征，极化程度大幅提升。目前，针对该电荷模型开发带有合适二面角参数的全新力场的工作正在推进中。IPolQ方法具有普适性，可应用于任意溶质体系。