Quantum Mechanical Electrostatic Potential Research Articles

Electronic structure properties of solvated biomolecules: A quantum approach for macromolecular characterization

Linear-scaling electronic structure calculations of solvated biomolecules have been carried out using a semiempirical Hamiltonian and a new smooth solvation potential. These methods afford a new way of generating macromolecular properties that include quantum electronic structure. In addition to the widely used classical electrostatic potential maps based on empirically derived static point charges, now fully quantum mechanical electrostatic potentials that include electronic polarization are possible. Linear-scaling electronic structure methods provide a host of response properties of the electron density such as linear response functions, local hardness functions, and Fukui functions. It is the hope that these indices will extend insight into problems of biological macromolecular characterization. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1562–1571, 2000

Prediction of inhibitor binding free energies by quantum neural networks. Nucleoside analogues binding to trypanosomal nucleoside hydrolase.

A computational method has been developed to predict inhibitor binding energy for untested inhibitor molecules. A neural network is trained from the electrostatic potential surfaces of known inhibitors and their binding energies. The algorithm is then able to predict, with high accuracy, the binding energy of unknown inhibitors. IU-nucleoside hydrolase from Crithidia fasciculata and the inhibitor molecules described previously [Miles, R. W. Tyler, P. C. Evans, G. Furneaux R. H., Parkin, D. W., and Schramm, V. L. (1999) Biochemistry 38, xxxx-xxxx] are used as the test system. Discrete points on the molecular electrostatic potential surface of inhibitor molecules are input to neural networks to identify the quantum mechanical features that contribute to binding. Feed-forward neural networks with back-propagation of error are trained to recognize the quantum mechanical electrostatic potential and geometry at the entire van der Waals surface of a group of training molecules and to predict the strength of interactions between the enzyme and novel inhibitors. The binding energies of unknown inhibitors were predicted, followed by experimental determination of K(i)() values. Predictions of K(i)() values using this theory are compared to other methods and are more robust in estimating inhibitory strength. The average deviation in estimating K(i)() values for 18 unknown inhibitor molecules, with 21 training molecules, is a factor of 5 x K(i)() over a range of 660 000 in K(i)() values for all molecules. The a posteriori accuracy of the predictions suggests the method will be effective as a guide for experimental inhibitor design.

Generation of OPLS-like charges from molecular electrostatic potential using restraints

A new method for generating atom-centered charges for use in condensed phase computer simulations is presented, which is based on a restrained electrostatic potential (RESP) procedure. Charges are calculated from a least-squares fit to the quantum mechanical electrostatic potential with a restraint applied to reduce their magnitude. The restraint developed here offers advantages over that used in RESP. The magnitude of the restraint is optimized to yield charges as close to the equivalent OPLS values as possible while still reproducing the molecule's electrostatic potential. A cross-validation analysis is used to show that the restraint is insensitive to the selection of OPLS molecules from which it is derived. Thus, with this method, OPLS-like charges may be produced from the electrostatic potential for atom types not in the OPLS force field. In addition, the restraint is shown to reduce the conformational dependence of the charges. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 483–498, 1999

Are There Water-Bridge-Induced Hydrophilic Interactions?

Inspired by experimental studies of the transfer free energies of phenol derivatives with hydroxylmethyl substitutions at ortho, meta, and para positions, Ben-Naim has proposed that water-bridge-induced “hydrophilic interactions” are stabilizing by about 3 kcal/mol, much larger than corresponding hydrophobic interactions. We have used theoretical free energy perturbation calculations to assess this proposal. By use of two sets of partial charge models derived by fitting to ab initio quantum mechanical electrostatic potentials, free energy calculations have shown that the solvation free energy differences between these substituted phenols are small. These results are inconsistent with the aforementioned “water-bridge” hypothesis. Interestingly, these calculated free energies for gas phase → water are quite consistent with the experimental values for octanol → water free energies of transfer but not with the experimental values for toluene → water free energies of transfer, which were used by Ben-Naim to de...

Theoretical studies on structure, thermochemistry, vibrational spectroscopy, and other features of ZrX2−6 (X=F,Cl,Br,I): Coulombic energy in inorganic and organic hexahalogenozirconates

The geometries of ZrX2−6 (X=F,Cl,Br,I) were optimized at the ab initio Hartree–Fock SCF level using all-electron MIDI and effective core potential valence basis sets of double-zeta quality, supplemented with diffuse functions. In addition, geometries and energies of X2, as well as energies of gaseous Zr were determined in order to predict energies of formation of ZrX2−6. Effects of electron correlation were taken into account at the second order Mo/ller–Plesset level of theory. Vibrational frequencies were determined in the harmonic approximation and compared with available experimental data. Standard routines were employed to evaluate entropies, heat capacities, heats of formation and free enthalpies of formation of gaseous ZrX2−6. Electrostatic cohesive energies in hexahalogenozirconates were evaluated by the extended Ewald method. It was assumed that each ion gathers a formal charge +1, +2, or −2. Net atomic charges in complex ions were determined either from various population analyses or fitted to the ab initio quantum mechanical electrostatic potential. The Coulombic energies decrease gradually with the increase in volume of the simplest structural unit. A similar tendency is noted as regards distances between interacting centers. Theoretically determined properties are in a good agreement with available data, mostly of experimental origin.

Molecular electrostatic potentials and partial atomic charges from correlated wave functions: Applications to the electronic ground and excited states of 3‐methylindole

AbstractProcedures have been developed to generate molecular electrostatic potentials based on correlated wave function from ab initio or semiempirical electronic structure programs. A new algorithm for point‐wise sampling of the potential is described and used to obtain partial atomic charges via a linear, least squares fit between classical and quantum mechanical electrostatic potentials. The proposed sampling algorithm is efficient and promises to introduce less rotational variance in the potential derived partial charges than algorithms applied previously. Electrostatic potentials and fitted atomic charges from ab initio (HF/6–31G* and MP2/6‐31G*) and semiempirical (INDO/S; HF, SECI, and SDCI) wave functions are presented for the electronic ground (S0) and excited (1Lb, 1La) states of 3‐methylindole. © 1992 by John Wiley & Sons, Inc.

Solvent effects on the adiabatic free energy difference between the ground and excited states of methylindole in water

Molecular dynamics simulations have been used to compute the adiabatic free energy difference between the electronic ground and 'L, excited states of 3-methylindole in water. Partial atomic charges for the two electronic states were derived from fits to the (gas phase) quantum mechanical electrostatic potentials produced by semiempirical INDO/S wave functions. The computed solvent reorganization energy (- 3 kcal/mol) is smaller than values deduced from experimental spectroscopic data for various indole derivatives in polar solvents (4-12 kcal/mol). The solvent reorganization energy computed from the simulations is close to the value estimated from the Onsager dipole cavity reaction field model when a previously suggested, but ad hoc, molecular volume parameter is used with the model. However, this model is shown to generally not approximate reaction field energies well for a large planar molecule like indole, since it does not distinguish among diffmnt charge distributions which produce the same change in the magnitude of the chromophore dipole moment but very different reaction fields. Additional free energy simulations are carried out to demonstrate this point. In contrast, a recently proposed molecular dielectric model, which explicitly incorporates the effects of the solute structure and charge on the solvent dielectric response, is found to agree with the simulated free energy changes to within a few percent.

A practical procedure for the determination of electrostatic charges of large molecules

A practical procedure for the precise determination of electrostatic charges, which are evaluated by fitting the rigorous quantum mechanical molecular electrostatic potential to a monopole-monopole expression, is presented. The proposal of this procedure arises from the study of the minimum requirements necessary to obtain reliable electrostatic charges. Such a study is focused on: (i) the dependence of the electrostatic charges on the set of points where the quantum mechanical and the monopole-monopole molecular electrostatic potentials are fitted; thus, both the influence of the number of points and their distribution in layers located out of the van der Waals radii of the atoms are examined, and (ii) the reliability of the use of fractional models for the evaluation of electrostatic charges of large molecules. Results point out that the optimum number of points is defined by a density of points ranging from 0.45 to 0.60 points/A2 when four layers (separated by 0.2 A) are considered. Nevertheless, the use of only two layers (separated by 0.4 A) for large molecules is recommended, thus enabling one to obtain reliable charges at a reduced computational cost. Moreover, results justify the use of fractional models for the determination of electrostatic charges of extremely large molecules, even when aromatic structures exist.

Study of the orientation of thiourea adsorbed on aluminum oxide by tunneling spectroscopy. II. Comparison of experimental and calculated intensities.

Experimental and calculated tunneling intensities were compared for several vibrational modes of thiourea [CS(${\mathrm{NH}}_{2}$${)}_{2}$] adsorbed on aluminum oxide. The partial charge model of Kirtley, Scalapino, and Hansma, as extended by the use of floating valence charges, was used to compute the theoretical intensities. The required partial charges on each atom were determined for each vibrational mode using a method developed by Momany and described in the preceding paper. The Coulomb potential resulting from point charges located at atom sites was fitted to the quantum-mechanical electrostatic potential of a molecule calculated from Hartree-Fock theory. Two charges were associated with each atomic site since an investigation of the effects of a vibrational mode pattern on the electrostatic potential of a molecule had shown that the potential could not be acceptably modeled with a single point charge located on each atom. One charge was used to represent the core charge of each atom and a second charge was used to represent the valence-charge cloud. In fitting the potential, the valence charge was allowed to move independently of the core charge during a molecular vibration. The motions of the two charges were found to be very different for hydrogen atoms. This ``floating-valence-charge'' model gave very reasonable agreement between the theoretical and observed relative intensities for the in-plane vibrational modes of thiourea. An acceptable set of out-of-plane force constants could not be found, which caused problems in the interpretation of the out-of-plane relative intensities.

Study of the orientation of thiourea adsorbed on aluminum oxide by tunneling spectroscopy. I. Determination of partial charges from molecular electrostatic potential calculations for thiourea and urea.

Ab initio electrostatic molecular potentials for urea [CO(${\mathrm{NH}}_{2}$${)}_{2}$] and thiourea [CS(${\mathrm{NH}}_{2}$${)}_{2}$] have been calculated with use of restricted Hartree-Fock theory. A nonlinear least-squares regression package was used to fit atomic partial charges to the potentials. Calculations were made with use of several different basis sets with and without polarization functions. Basis-set scaling factors calculated for each atom showed that the potential-derived (PD) charges were much more reliable than the Mullikan values. The effects of a vibrational mode on the calculated partial charges were also evaluated. Dipole moments were calculated with use of various basis sets and compared with observed values. The potential was also fitted by splitting the static charge determined for each atomic site into two portions. The core-charge portion was forced to follow the nuclear motion, whereas the valence-charge portion was allowed to float in a direction such that the best fit to the potential was obtained. This latter procedure provided reproductions of the calculated quantum-mechanical electrostatic potentials which were determined to be sufficiently accurate for electron-tunneling-intensity calculations. Comparison of experimental and calculated tunneling intensities for thiourea are presented in the following paper.

Comments on the electronic structure and reactivity of chromones

AB initio calculations of ground-state wavefunctions of chromones and thiochromones have been carried out and correlated with the observed reactivity of these molecules. Quantum mechanical electrostatic potentials correctly predict nucleophilic attack to occur preferentially at C-2 and C-4 in chromones and thiochromones respectively. Frontier-orbital considerations correctly predict the site selectivity of the photochemical cycloaddition to the pyrone double bond of chromone.

Representation of the molecular electrostatic potential by a net atomic charge model

AbstractElectrostatic potentials and Mulliken net atomic charges were calculated from STO‐3G, 6‐31G, and 6‐31G** SCF‐MO wavefunctions for hydrogen fluoride, water, ammonia, methane, acetylene, ethylene, carbon dioxide, formaldehyde, methanol, formamide, formic acid, acetonitrile, diborane, and carbonate ion. In each case optimized net atomic charges (potential‐derived charges) were also obtained by fitting the electrostatic potentials calculated directly from the wavefunctions in a shell enveloping the molecules outside of their van der Waals surfaces. The electrostatic potentials calculated from the potential‐derived charge distributions were then compared with the defined quantum mechanical electrostatic potentials and with the electrostatic potentials of the Mulliken charge distributions.