The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.

Potentials of mean force (PMF) between all possible ionizable amino acid side chain pairs in various protonation states were calculated using explicit solvent molecular dynamics simulations with umbrella sampling and the weighted histogram analysis method. The side chains were constrained in various orientations inside a spherical cluster of 200 water molecules. Beglov and Roux's Spherical Solvent Boundary Potential was used to account for the solvent outside this sphere. This approach was first validated by calculating PMFs between monatomic ions (K(+), Na(+), Cl(-)) and comparing them to results from the literature and results obtained using Ewald summation. The strongest interaction (-4.5 kcal/mol) was found for the coaxial Arg(+).Glu(-) pair. Many like-charged side chains display a remarkable lack of repulsion, and occasionally a weak attraction. The PMFs are compared to effective energy curves obtained with common implicit solvation models, namely Generalized Born (GB), EEF1, and uniform dielectric of 80. Overall, the EEF1 curves are too attractive, whereas the GB curves in most cases match the minima of the PMF curves quite well. The uniform dielectric model, despite some fortuitous successes, is grossly inadequate.

In this benchmark study, time-dependent density-functional theory (TDDFT) is applied to calculate one-and two-photon absorption spectra (related to linear and third-order optical responses, respectively) in a series of large donor-acceptor substituted conjugated molecules. Calculated excitation energies corresponding to oneand two-photon-absorption maxima are found to be in excellent agreement with experiment. The evaluated two-photon-absorption cross sections agree with experimental data as well. We conclude that the TDDFT approach is a numerically efficient method for quantitative calculations of resonant nonlinear polarizabilities in large organic chromophores.

Molecular orbital calculations on methane, acetylene, and HCN in electric fields of various strengths have been performed at the HF/D95** level. The molecules were oriented in the field so that one C−H bond was aligned with the field in the direction appropriate for a stabilizing polarization of that bond. Although the C−H bonds of acetylene and HCN lengthen as the field increases, that of methane shortens until the field reaches 0.02 au then lengthens as the field is further increased. Electron density analyses using three different methods (Mulliken populations, Natural Bond Orbitals, and Atoms in Molecules) all show a shift of electron density from the putative H-bonding hydrogen toward the bulk of the molecule (although they disagree with each other in several other ways). We interpret the data to suggest that the hydrogen in methane is electron rich with respect to the carbon (in contrast to those of HCN and acetylene). At small electric fields, electron density from the hydrogen moves into the C−H bond, both strengthening and shortening it. When the electric field increases beyond 0.02 au, net electron density starts to move from the C−H bond toward the carbon causing the bond to begin to weaken and lengthen. The C−H bonds of HCN and acetylene both lengthen as the field is increased. The behavior of all three molecules in the fields is sufficient to explain their H-bonding behavior.

The free energy of binding of a ligand to a macromolecule is here formally decomposed into the (effective) energy of interaction, reorganization energy of the ligand and the macromolecule, conformational entropy change of the ligand and the macromolecule, and translational and rotational entropy loss of the ligand. Molecular dynamics simulations with implicit solvation are used to evaluate these contributions in the binding of biotin, biotin analogs, and two peptides to avidin and streptavidin. We find that the largest contribution opposing binding is the protein reorganization energy, which is calculated to be from 10 to 30 kcal/mol for the ligands considered here. The ligand reorganization energy is also significant for flexible ligands. The translational/rotational entropy is 4.5–6 kcal/mol at 1 M standard state and room temperature. The calculated binding free energies are in the correct range, but the large statistical uncertainty in the protein reorganization energy precludes precise predictions. For some complexes, the simulations show multiple binding modes, different from the one observed in the crystal structure. This finding is probably due to deficiencies in the force field but may also reflect considerable ligand flexibility. Proteins 2002;47:194–208. © 2002 Wiley‐Liss, Inc.

One-dimensional hydrogen-bonding aggregates of urea and thiourea corresponding to the two patterns, chains and ribbons, which are found in crystal structures of these molecules have been studied using ab initio and semiempirical molecular orbital theory. In accord with experimental evidence, long chains are found to be more stable than comparably sized ribbons for urea, although ribbons are favored for dimers and small aggregates. Thiourea ribbons are favored over chains for all aggregates, large and small, again in agreement with the experimental crystal structure. Thus, cooperative interactions dictate the hydrogen-bonding structure for urea, but not thiourea, crystals. Various ab initio (HF, MP2, and B3PW91 all the with the D95** basis set) and semiempirical (AM1 and SAM1) molecular orbital calculations were used for this study.

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The donor/acceptor (D/A) substituted pi-conjugated organic molecules possess extremely fast nonlinear optical (NLO) response time that is purely electronic in origin. This makes them promising candidates for optoelectronic applications. In the present study, we utilized four hybrid density functionals (B3LYP, B97-2, PBE0, BMK), Hartree-Fock, and second order Moller-Plesset correlation energy correction, truncated at second-order (MP2) methods with different basis sets to estimate molecular first hyperpolarizability (beta) of D/A-substituted benzenes and stilbenes (D=OMe, OH, NMe(2), NH(2); A=NO(2), CN). The results of density functional theory (DFT) calculations are compared to those of MP2 method and to the experimental data. We addressed the following questions: (1) the accurate techniques to compare calculated results to each other and to experiment, (2) the choice of the basis set, (3) the effect of molecular planarity, and (4) the choice of the method. Comparison of the absolute values of hyperpolarizabilities obtained computationally and experimentally is complicated by the ambiguities in conventions and reference values used by different experimental groups. A much more tangible way is to compare the ratios of beta's for two (or more) given molecules of interest that were calculated at the same level of theory and measured at the same laboratory using the same conventions and reference values. Coincidentally, it is the relative hyperpolarizabilities rather than absolute ones that are of importance in the rational molecular design of effective NLO materials. This design includes prediction of the most promising candidates from particular homologous series, which are to be synthesized and used for further investigation. In order to accomplish this goal, semiquantitative level of accuracy is usually sufficient. Augmentation of the basis set with polarization and diffuse functions changes beta by 20%; however, further extension of the basis set does not have significant effect. Thus, we recommend 6-31+G(*) basis set. We also show that the use of planar geometry constraints for the molecules, which can somewhat deviate from planarity in the gas phase, leads to sufficient accuracy (with an error less than 10%) of predicted values. For all the molecules studied, MP2 values are in better agreement with experiment, while DFT hybrid methods overestimate beta values. BMK functional gives the best agreement with experiment, with systematic overestimation close to the factor of 1.4. We propose to use the scaled BMK results for prediction of molecular hyperpolarizability at semiquantitative level of accuracy.