Additive and Classical Drude Polarizable Force Fields for Linear and Cyclic Ethers

Abstract

Empirical force field parameters consistent with the CHARMM additive and classical Drude based polarizable force fields are presented for linear and cyclic ethers. Initiation of the optimization process involved validation of the aliphatic parameters based on linear alkanes and cyclic alkanes. Results showed the transfer to cyclohexane to yield satisfactory agreement with target data; however, in the case of cyclopentane direct transfer of the Lennard-Jones parameters was not sufficient due to ring strain, requiring additional optimization of these parameters for this molecule. Parameters for the ethers were then developed starting with the available aliphatic parameters, with the nonbond parameters for the oxygens optimized to reproduce both gas- and condensed-phase properties. Nonbond parameters for the polarizable model include the use of an anisotropic electrostatic model on the oxygens. Parameter optimization emphasized the development of transferable parameters between the ethers of a given class. The ether models are shown to be in satisfactory agreement with both pure solvent and aqueous solvation properties, and the resulting parameters are transferable to test molecules. The presented force field will allow for simulation studies of ethers in condensed phase and provides a basis for ongoing developments in both additive and polarizable force fields for biological molecules.