A new intermolecular force field for nitrogen atoms in organic molecules was derived from a training dataset of 76 observed azahydrocarbon crystal structures and 11 observed heats of sublimation. The previously published W99 force field for hydrogen, carbon, and oxygen was thus extended to include nitrogen atoms. Nitrogen atoms were divided into four classes: N(1) for triply bonded nitrogen, N(2) for nitrogen with no bonded hydrogen (except the triple bonded case), N(3) for nitrogen with one bonded hydrogen, and N(4) for nitrogen with two or more bonded hydrogens. H(4) designated hydrogen bonded to nitrogen. Wavefunctions of 6-31g** quality were calculated for each molecule and the molecular electric potential (MEP) was modeled with net atomic and supplementary site charges. Lone pair electron charge sites were included for nitrogen atoms where appropriate, and methylene bisector charges were used for CH2 and CH3 groups when fitting the MEP. XH bond distances were set to standard values for the wave function calculation and then foreshortened by 0.1 A for the MEP and force field fitting. Using the force field optimized to the training dataset, each azahydrocarbon crystal structure was relaxed by intermolecular energy minimization. Predicted maximum changes in unit cell edge lengths for each crystal were 3% or less. The complete force field for H, C, N, and O atoms was tested by intermolecular energy relaxation of nucleoside and peptide molecular crystals. Even though these molecules were not included in any of the training datasets for the force field, agreement with their observed crystal structures was very good, with predicted unit cell edge shifts usually less than 2%. These tests included crystal structures of representatives of all eight common nucleosides found in DNA and RNA, 15 dipeptides, four tripeptides, two tetrapeptides, and a pentapeptide with two molecules in the asymmetric unit. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1154–1166, 2001

Improved intermolecular force field for molecules containing H, C, N, and O atoms, with application to nucleoside and peptide crystals

Publisher Summary This chapter introduces the potential-derived point charge least-squares fitting model for the electric potential (PD/LSF model) to persons who are interested in it in detail. To establish the PD/LSF point-charge model of a molecule, the first step is to calculate the electric potential at point “r” in vicinity of the given molecule, and the second step is to calculate point charges from the electric potential data by means of the least-squares fitting method. The electric potential at point “r” in the vicinity of the given molecule is the electric force acting on a unit positive charge at that point caused by the nuclei and the electrons of the molecule. The atomic orbital is always modeled by the Gaussian-type functions. In some cases, the programs have capability for obtaining an improved wave function including the effects of electron correlation. The electric potential may be evaluated from the wave function at points in space around the molecule.

Point-Charge Models for Molecules Derived from Least-Squares Fitting of the Electric Potential

Improved intermolecular force field for crystalline hydrocarbons containing four- or three-coordinated carbon

An improved intermolecular force field of the (exp-6-1) type was obtained by fitting a training set of 124 observed oxohydrocarbon crystal structures and seven observed heats of sublimation. All of these structures, when energy minimized, showed cell edge length shifts of 3% or less. Especially good results were obtained for modeling carbohydrate crystal structures. The fitted crystal structures are a subset of a database of 180 structures systematically selected from the CSD library according to functional group and threshold accuracy criteria. Energy minimization results are also presented for 56 structures not in the training set, which showed cell edge length shifts larger than 3%. The previously published W99 force field, using C(4), C(3), and H(1) potentials, was slightly modified and adopted for hydrocarbon portions of the molecules. Oxygen atoms with one bond, O(1), and those with two bonds, O(2), were assigned separate parameters. Hydrogen atoms bonded to oxygen were assigned exponential repulsion functions and divided into two types: in hydroxy groups, H(2); and in carboxyl groups, H(3). Wavefunctions of HF 6-31g** quality were calculated for every molecule and the molecular electric potential (MEP) was modeled with net atomic charges. Methylene bisector charges were used for all CH2 and CH3 groups, and ring center site charges were added if necessary to fit the MEP. For some structures, upward scaling of the MEP to simulate intermolecular polarization gave better results. MEP interaction generally gave a satisfactory representation of weak CHO hydrogen bonding. Medium strength CHO hydrogen bonding was modeled by reducing the repulsion of the involved hydrogen atoms. Crystal structures of several biologically interesting molecules were modeled with the force field, yielding good results. These molecules include aspirin, sucrose, β-cellobiose, β-lactose, progesterone, testosterone, prostaglandin E1, cholesterol acetate, and stearic acid. © 2000 John Wiley & Sons, Inc. J Comput Chem 22: 1–20, 2001

Improved intermolecular force field for crystalline oxohydrocarbons including OHO hydrogen bonding

Empirical nonbonded atom parameters can be developed for dispersion, repulsion, and Madelung’s (Coulombic) lattice potential energies of a few reference organic crystals, whose crystal structures and experimental lattice energies are known. A review is given of the relevant mathematical procedures (Ewald’s accelerated convergence of lattice sums, force-fit and direct-parameter-fit methods).

Transferable Empirical Nonbonded Potential Functions

Three empirical potential models (dumbbell, Kihara, and ellipsoidal overlap) are fitted to theoretical calculations of H2–H2 and H2–He repulsion. The dumbbell model gives a slightly better fit and has better transferability. This model is recommended because of its simplicity and physical meaningfulness.

D. E. Williams

Papers

Comparison of models for H2–H2 and H2–He anisotropic intermolecular repulsion