TY - JOUR
T1 - Computation of hydration free energies using the multiple environment single system quantum mechanical/molecular mechanical method
AU - König, Gerhard
AU - Mei, Ye
AU - Pickard, Frank C.
AU - Simmonett, Andrew C.
AU - Miller, Benjamin T.
AU - Herbert, John M.
AU - Woodcock, H. Lee
AU - Brooks, Bernard R.
AU - Shao, Yihan
N1 - authored in non-UK institution, in USA
PY - 2016/1/12
Y1 - 2016/1/12
N2 - A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.
AB - A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.
UR - http://www.scopus.com/inward/record.url?scp=84954414283&partnerID=8YFLogxK
U2 - 10.1021/acs.jctc.5b00874
DO - 10.1021/acs.jctc.5b00874
M3 - Article
C2 - 26613419
AN - SCOPUS:84954414283
SN - 1549-9618
VL - 12
SP - 332
EP - 344
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 1
ER -