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.