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

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. XH bond distances were set to standard values for the wave function calculation and then foreshortened by 0.1 Å 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

[1]  S. Lifson,et al.  Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 1. Carboxylic acids, amides, and the C:O.cntdot..cntdot..cntdot.H- hydrogen bonds , 1979 .

[2]  D. E. Williams,et al.  Ab initio molecular packing analysis , 1996 .

[3]  Donald E. Williams,et al.  Representation of the molecular electrostatic potential by a net atomic charge model , 1981 .

[4]  P Verwer,et al.  A test of crystal structure prediction of small organic molecules. , 2000, Acta crystallographica. Section B, Structural science.

[5]  D. E. Williams,et al.  Comparison of models for H2–H2 and H2–He anisotropic intermolecular repulsion , 1977 .

[6]  D. E. Williams,et al.  Nonbonded potentials for azahydrocarbons: the importance of the Coulombic interaction , 1984 .

[7]  R. K. McMullan,et al.  The crystal structure and molecular thermal motion of urea at 12, 60 and 123 K from neutron diffraction , 1984 .

[8]  Donald E. Williams,et al.  Failure of net atomic charge models to represent the van der Waals envelope electric potential of n‐alkanes , 1994, J. Comput. Chem..

[9]  Gao,et al.  Molecular packing groups and ab initio crystal-structure prediction. , 1999, Acta crystallographica. Section A, Foundations of crystallography.

[10]  Donald E. Williams,et al.  Lone-pair electronic effects on the calculated ab initio SCF-MO electric potential and the crystal structures of azabenzenes , 1983 .

[11]  Donald E. Williams.  Molecular packing analysis , 1972 .

[12]  Aleksandr Isaakovich Kitaĭgorodskiĭ,et al.  Molecular Crystals and Molecules , 1973 .

[13]  Donald E. Williams.  Improved intermolecular force field for crystalline oxohydrocarbons including OHO hydrogen bonding , 2001 .

[14]  D. E. Williams,et al.  Improved intermolecular force field for crystalline hydrocarbons containing four- or three-coordinated carbon , 1999 .

[15]  D. E. Williams,et al.  Transferable Empirical Nonbonded Potential Functions , 1981 .

[16]  Aron Abraha,et al.  Site charge models for molecular electrostatic potentials of cycloalkanes and tetrahedrane , 1999, J. Comput. Chem..

[17]  Terry R. Stouch,et al.  Characterization of force fields for lipid molecules: Applications to crystal structures , 1993, J. Comput. Chem..