Solvated ensemble averaging in the calculation of partial atomic charges

In the calculation of partial atomic charges, for use in molecular mechanics or dynamics simulations, it is common practice to select only a single conformation for the molecule of interest. For molecules that contain rotatable bonds, it is preferable to compute the charges from several relevant conformations. We present here results from a charge derivation protocol that determines the partial charges by averaging charges computed for conformations selected from explicitly solvated MD simulations, performed under periodic boundary conditions. This approach leads to partial charges that are weighted by a realistic population of conformations and that are suitable for condensed phase simulations. This protocol can, in principle, be applied to any class of molecule and to nonaqueous solvation. Carbohydrates contain numerous hydroxyl groups that exist in an ensemble of orientations in solution, and in this report we apply ensemble averaging to a series of methyl glycosides. We report the extent to which ensemble averaging leads to charge convergence among the various monosaccharides and among the constituent atoms within a given monosaccharide. Due to the large number of conformations (200) in our ensembles, we are able to compute statistically relevant standard deviations for the partial charges. An analysis of the standard deviations allows us to assess the extent to which equivalent atom types may, nevertheless, require unique partial charges. The configurations of the hydroxyl groups exert considerable influence on internal energies, and the limits of ensemble averaged charges are discussed in terms of these properties. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1125–1137, 2001

[1]  Donald G. Truhlar,et al.  Quantum Chemical Conformational Analysis of Glucose in Aqueous Solution , 1993 .

[2]  G. A. Jeffrey,et al.  The crystal and molecular structure of methyl -D-glucopyranoside hemihydrate , 1977 .

[3]  Christian Pedersen,et al.  Carbon-13 Nuclear Magnetic Resonance Spectroscopy of Monosaccharides , 1983 .

[4]  Giuseppe Zerbi,et al.  Ab initio counterpart of infrared atomic charges , 1987 .

[5]  P Coppens,et al.  Electron Density from X-Ray Diffraction , 1992 .

[6]  Robert J. Woods,et al.  Derivation of net atomic charges from molecular electrostatic potentials , 1990 .

[7]  Jonathan W. Essex,et al.  Theoretical determination of partition coefficients , 1992 .

[8]  David M. Gange,et al.  Charges fit to electrostatic potentials. II. Can atomic charges be unambiguously fit to electrostatic potentials? , 1996 .

[9]  Ming-Jing Hwang,et al.  Derivation of class II force fields. I. Methodology and quantum force field for the alkyl functional group and alkane molecules , 1994, J. Comput. Chem..

[10]  Hiroshi Ohrui,et al.  1H-NMR studies of (6r)- and (6s)-deuterated d-hexoses: assignment of the preferred rotamers about C5C6 bond of D-glucose and D-galactose derivatives in solutions , 1984 .

[11]  F. Weinhold,et al.  Natural population analysis , 1985 .

[12]  R. Woods,et al.  Restrained electrostatic potential atomic partial charges for condensed-phase simulations of carbohydrates. , 2000, Theochem.

[13]  Donald E. Williams,et al.  Alanyl dipeptide potential‐derived net atomic charges and bond dipoles, and their variation with molecular conformation , 1990 .

[14]  G. A. Jeffrey,et al.  A neutron diffraction study of the hydrogen bonding in the crystal structures of methyl α-d-mannopyranoside and methyl α-d-glucopyranoside , 1977 .

[15]  Benjamin Bederson,et al.  Advances in atomic and molecular physics , 1965 .

[16]  William L. Jorgensen,et al.  OPLS all‐atom force field for carbohydrates , 1997 .

[17]  S H Kim,et al.  Determinations of atomic partial charges for nucleic acid constituents from x‐ray diffraction data. I. 2′‐Deoxycytidine‐5′‐monophosphate , 1985, Biopolymers.

[18]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[19]  R. Woods,et al.  Relative energies of binding for antibody-carbohydrate-antigen complexes computed from free-energy simulations. , 2000, Journal of the American Chemical Society.

[20]  C. Breneman,et al.  Determining atom‐centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis , 1990 .

[21]  Per-Olov Löwdin,et al.  On the Nonorthogonality Problem , 1970 .

[22]  W. Goddard,et al.  Charge equilibration for molecular dynamics simulations , 1991 .

[23]  Terry R. Stouch,et al.  Conformational dependence of electrostatic potential derived charges of a lipid headgroup: Glycerylphosphorylcholine , 1992 .

[24]  R. S. Mulliken Electronic Population Analysis on LCAO–MO Molecular Wave Functions. I , 1955 .

[25]  Owen Johnson,et al.  The development of versions 3 and 4 of the Cambridge Structural Database System , 1991, J. Chem. Inf. Comput. Sci..

[26]  Richard F. W. Bader,et al.  Bonded and nonbonded charge concentrations and their relation to molecular geometry and reactivity , 1984 .

[27]  P. Kollman,et al.  Application of RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation , 1993 .

[28]  P. Kollman,et al.  Atomic charges derived from semiempirical methods , 1990 .

[29]  L. E. Chirlian,et al.  Atomic charges derived from electrostatic potentials: A detailed study , 1987 .

[30]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[31]  Jonathan W. Essex,et al.  Atomic charges for variable molecular conformations , 1992 .

[32]  Robert J. Woods,et al.  Molecular Mechanical and Molecular Dynamic Simulations of Glycoproteins and Oligosaccharides. 1. GLYCAM_93 Parameter Development , 1995 .