We present self-consistent reaction field (SCRF) calculations,
utilizing correlated ab initio quantum mechanics,
of aqueous solvation free energies for a large data base of molecular
solutes. We identify a subset of chemical
functional groups for which there are systematic deviations in the
comparison of theory and experiment;
furthermore, for one case which has been extensively investigated,
methylated amines, similar deviations
appear in explicit solvent free energy perturbation calculations
employing several commonly used molecular
mechanics potential functions. By carrying out high-level ab
initio quantum chemical calculations of hydrogen-bonding energies of the solutes to a water molecule, we arrive at a
coherent explanation of the disagreements
between theory and experiment, namely, that hydrogen-bonding energies
are in some cases poorly correlated
with classical electrostatic interaction energies. We show that
the deviation in hydrogen-bonding energies of
a solute from a reference molecule (for which there is good agreement
between the SCRF calculations and
experiment) is an excellent predictor of the errors made for that
solute in the SCRF calculations. A new
SCRF model is developed in which short-range empirical corrections,
based upon solvent accessibility, are
made for these chemical functional groups; this reduces the mean error
of the calculated solvation free energies
for the entire data base by a factor of ∼2, to 0.37 kcal/mol.
These results have significant implications for
the accuracy of explicit solvent potential functions as well as
dielectric continuum models. Finally, we also
identify cases where the observed discrepancies in solvation free
energies cannot be explained by pair hydrogen-bonding results and suggest problems here that may be specific to
dielectric continuum theory.
We discuss computational methods for carrying out correlated ab initio electronic structure calculations for large systems. The focus is on two types of methods: density functional theory (DFT) and localized orbital methods such as local MP2 (LMP2) and a multireference version based upon a generalized valence bond reference wave function, GVB-LMP2. The computational performance of both approaches using pseudospectral numerical methods is documented, and calculated thermochemical and conformational energetics are compared to experimental data.
We have developed an algorithm based upon pseudospectral ab initio electronic structure methods for evaluating correlation energies via the localized Mo "ller-Plesset methodology of Pulay and Saebo. Even for small molecules (ϳ20 atoms͒ CPU times are diminished by a factor of ϳ10 compared to canonical MP2 timings for Gaussian 92 and the scaling is reduced from N 4 ϪN 5 in conventional methods to ϳN 3. We have tested the accuracy of the method by calculating conformational energy differences for 36 small molecules for which experimental data exists, using the Dunning cc-pVTZ correlation consistent basis set. After removing 6 test cases on the grounds of unreliability of the experimental data, an average deviation with experiment of 0.18 kcal/mol between theory and experiment is obtained, with a maximum deviation of ϳ0.55 kcal/mol. This performance is significantly better than that obtained previously with a smaller basis set via canonical MP2; it is also superior to the results of gradient corrected density functional theory.
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