Charge calculations in molecular mechanics. Part 8 Partial atomic charges from classical calculations

Summary The CHARGE2 programme, which involves the classical calculation of both the inductive and resonance contributions to the partial atomic charges in molecules is described, and the charges and electrostatic potentials obtained presented for some illustrative examples.In substituted methanes (CH₃X, CF₃X, CCl₃X) the effects of varying the electronegativity of the substituents and the - and -substituent contributions are clearly illustrated for a variety of substituent groups X.The problems involved in the inclusion of silicon into this scheme are detailed, together with the methods of overcoming them. The partial atomic charges ( and contributions) and electrostatic potentials for some silicon oxygen compounds are presented and discussed.The partial atomic charges from CHARGE2 for all the natural amino acids as their N-acetyl, N-methyl-amides are given and compared with those obtained from the AMBER and ECEPP/2 force fields. Considerable differences in these figures are observed, with the AMBER charges consistently much larger than those from the other two methods.The CHARGE2 partial atomic charges and electrostatic potentials for the four common nucleic acids, adenine, cytosine, guanine and thymine, are given and compared with those derived from other calculations. Again there is general similarity but also there are considerable differences, with those from the AMBER force field somewhat larger than the other methods.For previous parts in this series, see Refs. 1-7.     

Charge calculations in molecular mechanics. V. Silicon compounds and π bonding

A previously published scheme for the calculation of partial atomic charges has been extended to include silicon, and has been parameterized for a range of Si? X bonds (X?C,H,O,F,Cl,Br). For the silicon–halogen and silicon–oxygen bonds, a comparison is made between charges calculated with and without the inclusion of π-bonding. An extensive data set consisting of experimental geometries and dipole moments for the silicon compounds considered is presented and this leads to the selection of standard Si? X bond lengths. The calculated dipole moments for the above compounds are in good agreement with those obtained experimentally only when the π charges are included. A comparison has also been made between the partial charges from this scheme and those obtained from computational methods using the Mulliken population analysis. There is considerable disagreement between the methods. Finally, the implications of the charges and structural data are considered in terms of application to zeolite systems.     

Uniform quality gaussian basis sets for molecular calculations. III. Charge optimized basis sets

Gradient optimized constrained (2s ≠ 2p) and unconstrained (2s ≠ 2p) Gaussian 3G basis sets are reported for the first-row atoms and ions X^O, for Q = ?2 to +4. Analytic equations have been fitted to the logarithm of the exponents as a function of the nuclear charge Z and formal charge Q. Consequently only two parameters Z and Q have to be specified in order to completely define a basis set.     

Second row molecular orbital calculations: III. Semi-empirical calculations of geometries

The ability of four semi-empirical methods to predict geometries of molecules containing atoms in the second row of the periodic table is investigated for about 80 molecules. Non-empirical, minimal basis set calculations, with and without optimization of valence orbital exponents, are carried out for a number of diatomic molecules. While none of the methods are capable of predicting geometries with an accuracy comparable to the first row parametrization, the SPD' method of Santry and the related INDO method of Benson and Hudson appear to be the most consistent. The ab initio calculations do not suffer from the drawbacks exhibited by the latter two semi-empirical methods. From this it is concluded that the failure of such methods lies in the parametrization rather than in the use of a minimal basis set.     

Molecular mechanics calculations on carbonyl compounds. III. Cycloketones

Molecular mechanics (MM4) calculations were carried out on cycloketones for ring sizes ranging from 4 to 11 carbon atoms. The MM4 relative energies for the various conformations of the cycloketones were compared to density functional theory (DFT) calculations (B3LYP/6‐31G*), which were also carried out in this work. For small ring sizes (n=4–6), calculated molecular geometries, dipole moments, moments of inertia, and vibrational spectra were compared to experimental data. The axial–equatorial energy differences in methyl‐substituted cyclohexanones were also calculated by MM4 and compared to ab initio, DFT, and experimental results. The results of the MM4 studies on cycloketones showed significant improvement from those of MM3 calculations performed in parallel with the MM4 calculations. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1451–1475, 2001     

Approaches to charge calculations in molecular mechanics

Alternative methods of estimating atomic charges in haloalkanes are presented, derived from quantum mechanical and classical treatments. A scheme based on a breakdown of the transmission of charge by polar atoms into one-bond, two-bond, and three-bond additive contributions is given, in which the one-bond effect is proportional to the difference in the electronegativities of the bonded atoms, and the two- and three-bond effects functions of the atomic electronegativity and polarizability. Suitable developments of the basic scheme, including an iterative self-consistent process, give calculated dipole moments for a variety of haloalkanes in good agreement with the observed values. The atomic charges obtained by this scheme are compared with other estimates of these charges. They are similar to those derived from a simple LCAO –MO scheme but differ from those obtained by population analysis of more refined quantum mechanical calculations.     

Forces in molecular recognition: Comparison of experimental data and molecular mechanics calculations

Summary NMR studies of the rotation barrier of the disaccharide of the glycopeptide antibiotic vancomycin have been used to test the performance of computer simulation techniques using molecular mechanics. In the absence of any solvated water, no correlation could be found between experiment and calculation. By introducing solvent water molecules into the binding region of the antibiotic, the NMR results could be simulated both qualitatively and quantitatively within experimental error without using massive computational resources.     

Charge calculations in molecular mechanics. IX. A general parameterisation of the scheme for saturated halogen,oxygen and nitrogen compounds

Summary The CHARGE2 program for the calculation of partial atomic charges has been amended to include bond parameters for a number of organic functional groups, including halogens, nitrogen and oxygen. These minor amendments to the original scheme produce dipole moments for the fluoro and chloro compounds which are in complete agreement with the observed values.The less complete data sets for the bromo and iodo compounds are also well reproduced, and the dipole moments of a variety of mixed halo compounds are now in better agreement with experiment than previously.The calculated dipole moments of the saturated nitrogen and oxygen compounds are now in much better agreement than in the original scheme, thus the revised parameterisation may be employed with confidence to predict the electrostatic energies of these compounds.Furthermore, the revised scheme now gives a precise proportionality between the charge on the proton in a CH group and the ¹H chemical shift of the corresponding proton, allowing the general prediction, in principle, of ¹H chemical shifts. In addition, attempts to include variable electronegativity in the effect are described for fluoro compounds.For part VIII see Ref. 1.     

MoBioTools: A toolkit to setup quantum mechanics/molecular mechanics calculations

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.     

1,4-Interactions in molecular mechanics calculations of Ethers

Van der Waals and electrostatic interactions are found to be insufficient for the calculation of conformational energies of ethers by molecular mechanics. Low order torsional potential functions must be added for the potential about C-O bonds. A onefold term necessary for the CCOC-fragment is interpreted to be a substitute for gauche interactions present in CCCC-, but missing in CCOC-fragments. For the COCO fragment the anomeric effect must be included explicitly as another torsional energy term, but no such term is required to stabilize the gauche conformation for OCCO. With the resulting ether force field the geometries and energies of model compounds, many of them 1,3-dioxanes, are calculated with good accuracy.     

Conformational analysis—CXIX : Charge distribution in the molecular mechanics method

The method originally proposed by Smith and Eyring for calculating dipole moments of molecules by taking into account the effect of induction and the polarizability of bonds has been extended from an adjacent-bond to an all-bond procedure.The method is applied to some simple mono- and dihalogen compounds. Total dipole moments are reasonably well calculated. The dipole moments of 1,2-diaxial dihalides are correctly calculated for the first time.     

Conformational analysis—CXVII : Methyl ethyl disulfide. Molecular mechanics and molecular orbital calculations

The conformation of methyl ethyl disulfide was investigated by molecular mechanics calculations using a recently developed force field for sulfur-containing alkanes. The results indicate that in the gas phase the molecule exists predominantly in two conformations, both with the CSSC dihedral angle gauche (84°), and the SSCC dihedral angle either gauche (72°) or trans (179°), and the methyl protons staggered. Ab initio molecular orbital calculations using an STO-3G basis set were employed to corroborate that these two conformations are of roughly equal stability, and that the next most stable conformation (by 0.6 kcal/mole) has the SSCC dihedral angle gauche (295°) with the terminal methyls proximal. In contrast to earlier CNDO/2 (spd) predictions, the SSCC cis conformer is the least stable, and no sizable attractive S?HC nonbonded interactions are discerned. Reasons for this are traced to a failure of the CNDO/2 method, which is especially serious when d orbitals are included in the basis set (spd) and the rigid rotor approximation is used. The present results are found to be consistent with recent electron diffraction, IR, Raman spectroscopic and X-ray diffraction data. The conformation of diethyl disulfide was also investigated by molecular mechanics calculations, and again gauche and trans SSCC arrangements are predicted to be preferred.     

Amino acids and peptides. XXVII. Synthesis of phytochelatin-related peptides and examination of their heavy metal-binding properties

Phytochelatin (PC)-related peptides were prepared by a conventional solution method and their heavy metal-binding properties were examined. Different from the Cu2+ and Cu+ -binding properties of metallothionein (MT)-related peptides, the Cu2+ and Cu+ -binding properties of PC-related peptides were fairly dependent on structure. It is of interest that gamma-Glu-Cys-Gly (glutathione) exhibited quite different Cu2+ and Cu+ -binding properties from those of other PC-related peptides and its binding abilities were comparable to those of MT-related peptides. The Cd2+ -binding properties of glutathione were similar to those of Cys, and the Cd2+ -binding abilities of PC-related peptides increased in proportion to the increase of gamma-Glu-Cys peptide unit.     

Prediction of polymer miscibility from molecular mechanics calculations

A new computational method is presented for the rapid estimation of polymer miscibility. The algorithm (coined FLEXIBLEND) uses molecular mechanics calculations on a pair of polymer segments and takes into account the effects of local chain flexibility to estimate heats of mixing. This paper shows miscibility predictions in agreement with experiment for blends of poly(ethyleneoxide) (PEO) with isotactic poly(propylene) (PP) as an immiscible system and of PEO with poly(acrylic acid) (PAA) as a miscible system.     

Amino acids and peptides. XXXIII. Synthesis of N-terminal epitope peptides of mammalian metallothioneins (MTs).

In order to determine the fine structure of the mammalian metallothionein (MT) epitope to a monoclonal anti-rat Zn-MT-II antibody (MT 189-14-7), N-terminal peptides of various lengths of mammalian metallothioneins (MTs) were synthesized by a conventional solution method using the newly developed beta-2-adamantylaspartate, and their immunological properties were examined. It was found that the N-terminal acetyl group was indispensable for the reaction with the monoclonal antibody and the N-terminally acetylated pentapeptide, Ac-Met-Asp-Pro-Asn-Cys-OH, was the smallest peptide which exhibited a significant reactivity with the antibody.     

Consistent treatment of inter- and intramolecular polarization in molecular mechanics calculations

A protocol is described for the treatment of molecular polarization in force field calculations. The resulting model is consistent in that both inter- and intramolecular polarization are handled within a single scheme. An analytical formula for removing intramolecular polarization from a set of atomic multipoles for an arbitrary static structure or conformation is given. With the help of the intramolecular polarization, these permanent atomic multipoles can then be applied in modeling alternative conformations of a molecule. Equipped with this simple technique, one can derive transferable electrostatic parameters for peptides and proteins using flexible model compounds such as dipeptides. The proposed procedure is tested for its ability to describe the electrostatic potential around various configurations of the N-methylacetamide dimer. The effect of different intramolecular polarization schemes on the accuracy of a force field model of the electrostatic potential of alanine dipeptide is investigated. A group-based scheme for including direct intramolecular polarization is shown to be most successful in accounting for the conformational dependence of electrostatic potentials.