(51f) Estimating Physicochemical Properties of Amino Acid Side Chain Analogs Using Expanded Ensemble Molecular Simulation Algorithm: An Assessment of Force Fields

Solvation free energies in 1-octanol for amino acid side chain analogs are calculated using expanded ensemble molecular dynamics algorithm at room temperature. A typical solvation free energy calculation using conventional molecular dynamics algorithm requires more than 20 independent production runs following an equal number of equilibration runs where the simulation time may vary depending on the number of atoms present in the solvent and solute molecules and the number of solvent molecules. In contrast, the relatively new expanded ensemble (EE) molecular dynamics algorithm has been found more efficient than that of thermodynamic integration method (TI) in calculating solvation free energies without compromising accuracy with only a single equilibration and production run.  OPLS-AA, GAFF, CGenFF, GROMOS, and TraPPE force fields are used to model both amino acid analogs and 1-octanol molecule. Calculated solvation free energies are compared with experimental data. Octanol/water partition coefficients and Henry’s law constants of amino acid side chains are estimated from the solvation free energies in water and in 1-octanol. Vapor pressures of different 1-octanol models are estimated from the self-solvation free energies calculated here. Having the vapor pressure data, the solubilities of amino acid side chain analogs are also predicted using the solvation free energy data. Comparison of the simulation data has been made with the available experimental data.