Conformational simulations of aqueous solvated alpha-conotoxin GI and its single disulfide analogues using a polarizable force field model

The solution conformation of alpha-conotoxin GI and its two single disulfide analogues are simulated using a polarizable force field in combination with the molecular fragmentation quantum chemical calculation. The polarizability is explicitly described by allowing the partial charges and fragment dipole moments to be variables, with values coming from the linear-scaling energy-based molecular fragmentation calculations at the B3LYP/6-31G(d) level. In comparison with the full quantum chemical calculations, the fragmentation approaches can yield precise ground-state energies, dipole moments, and static polarizabilities for peptides. The B3LYP/6-31G(d) charges and fragment-centered dipole moments are introduced in calculations of electrostatic terms in both AmberFF03 and OPLS force fields. Our test calculations on the gas-phase glucagon (PDB code: 1gcn) and solvated alpha-conotoxin GI (PDB code: 1not) demonstrate that the present polarization model is capable of describing the structural properties (such as the relative conformational energies, intramolecular hydrogen bonds, and disulfide bonds) with accuracy comparable to some other polarizable force fields (ABEEM/MM and OPLS-PFF) and the quantum mechanics/molecular mechanics (QM/MM) hybrid model. The employment of fragment-centered dipole moments in calculations of dipole-dipole interactions can save computational time in comparison with those polarization models using atom-centered dipole moments without much loss of accuracy. The molecular dynamics simulations using the polarizable force field demonstrate that two single disulfide GI analogues are more flexible and less structured than the native alpha-conotoxin GI, in agreement with NMR experiments. The polarization effect is important in simulations of the folding/unfolding process of solvated proteins.     

Determination of net atomic charges using a modified partial equalization of orbital electronegativity method. III. Application to halogenated and aromatic molecules

The net atomic charge parameters for halogen atoms and the atoms in aromatic molecules have been determined by the modified partial equalization of orbital electronegativity method. The same parameters are used for the halogen atoms both in aromatic and nonaromatic systems. The calculated dipole moments of haloalkanes agree well with experiment, but those of the halogenated aromatic molecules do not reproduce the experimental values as well as those of the haloalkanes; in particular, the computed dipole moments for monohalogenated benzenes are all lower than the experimental values because of the influence of the lonepair electrons on the halogens. Within the limitations of an atom-centered point-charge approximation, our calculated dipole moments, both for haloalkanes and halogented aromatic molecules, agree well with experimental values. © John Wiley & Sons, Inc.     

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     

Molecular mechanics (MM4) calculations on carbonyl compounds part I: aldehydes

Aliphatic aldehydes have been studied with the aid of the MM4 force field. The structures, moments of inertia, vibrational spectra, conformational energies, barriers to internal rotation, and dipole moments have been examined for six compounds (nine conformations). MM4 parameters have been developed to fit the indicated quantities to the wide variety of experimental data. Ab initio (MP2) and density functional theory (B3LYP) calculations have been used to augment and/or replace experimental data, as appropriate. Because more, and to some extent, better, data have become available since MM3 was developed, it was anticipated that the overall accuracy of the information calculated with MM4 would be better than with MM3. The best single measure of the overall accuracy of a force field is the accuracy to which the moments of inertia of a set of compounds (from microwave spectroscopy) can be reproduced. For all of the 20 moments (seven conformations) experimentally known for the aldehyde compounds, the MM4 rms error is 0.30%, while with MM3, the most accurate force field presently available, the rms error over the same set is 1.01%. The calculation of the vibrational spectra was also improved overall. For the four aldehydes that were fully analyzed (over a total of 78 frequencies), the rms errors with MM4 and MM3 are 18 and 38 cm^?1, respectively. These improvements came from several sources, but the major ones were separate parameters involving the carbonyl carbon for formaldehyde, the alkyl aldehydes and the ketones, and new crossterms featured in the MM4 force field that are not present in the MM3 version. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1396–1425, 2001     

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.     

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.     

Non-empirical quantum chemical calculations of the structure of a homologous series of N-alkylpyridinium cations

The results of non-empirical quantum chemical calculations of geometric parameters, total energies, partial atomic charges, dipole moments, energies of frontier molecular orbitals obtained within second order Möller-Plesset perturbation theory in the MP2/6-31G(d,p) approximation are presented for a homologous series of N-alkyl pyridinium cations containing from 1 to 16 carbon atoms in the hydrocarbon radical. Differences are found in the electronic structure of lower and higher homologues.     

用第一性原理方法获取周期体系中原子的部分电荷

利用量子化学软件包Crystal计算了立方周期性边界条件下液态水体系的静电势(ESP)和静电场(EF).在此基础上,提出了一种由第一性原理方法获取周期体系中原子的部分电荷的快捷方法.该方法把由周期性边界条件引入的平均静电势准mean作为一个拟合参数,通过对第一性原理静电势与Ewald加和法静电势的最小二乘法拟合而实现.值得说明的是,比较静电势与静电场拟合方法,前者的相对拟合误差仅为2%-3%,比后者小一个数量级.考察了四种电荷限制条件下,静电势、静电场拟合的水分子原子部分电荷及偶极矩的分布情况.     

Class IV charge models: A new semiempirical approach in quantum chemistry

Summary We propose a new criterion for defining partial charges on atoms in molecules, namely that physical observables calculated from those partial charges should be as accurate as possible. We also propose a method to obtain such charges based on a mapping from approximate electronic wave functions. The method is illustrated by parameterizing two new charge models called AM1-CM1A and PM3-CM1P, based on experimental dipole moments and, respectively, on AM1 and PM3 semiempirical electronic wave functions. These charge models yield rms errors of 0.30 and 0.26 D, respectively, in the dipole moments of a set of 195 neutral molecules consisting of 103 molecules containing H, C, N and O, covering variations of multiple common organic functional groups, 68 fluorides, chlorides, bromides and iodides, 15 compounds containing H, C, Si or S, and 9 compounds containing C-S-O or C-N-O linkages. In addition, partial charges computed with this method agree extremely well with high-level ab initio calculations for both neutral compounds and ions. The CM1 charge models provide a more accurate point charge representation of the dipole moment than provided by most previously available partial charges, and they are far less expensive to compute.     

Ab initio valence bond calculations. VII. HF,HF+, and H2F+

Ab initio valence bond calculations for the ground and excited states of HF and HF⁺ are presented. Total energies, equilibrium geometries, dissociation energies, dipole moments, and spectroscopic constants for HF and HF⁺ have been calculated. The photoelectron spectrum of HF has been examined and interpreted by means of the valence bond formalism. The ground state of the protonated species H₂F⁺ has been investigated.     

Building molecular charge distributions from fragments: Application to HIV-1 protease inhibitors

Interaction energies are a function of the molecular charge distribution. In previous work, we found that the set of atomic partial charges giving the best agreement with experimental vacuum dipole moments were from density functional theory calculations using an extended basis set. Extension of such computations to larger molecules requires an atomic partial charge calculation beyond present computational resources. A solution to this problem is the calculation of atomic partial charges for segments of the molecule and reassociation of such fragments to yield partial charges for the entire molecule. Various partitions and reassociation methods for five molecules relevant to HIV-1 protease inhibitors are examined. A useful method of reassociation is introduced in which atomic partial charges for a large molecule are computed by fitting to the combined electrostatic potential calculated from the fragment partial charges. As expected, the best sites for partitions are shown to be carbon—carbon rather than carbon—nitrogen bonds. © 1997 by John Wiley & Sons, Inc.     

Comparison of the Hartree-Fock,Møller-Plesset,and Hartree-Fock-Slater method with respect to electrostatic properties of small molecules

Summary The results of various quantum chemical calculations, the Hartree-Fock (HF) method, the Møller-Plesset perturbation theory (MP2), and the Hartree-Fock-Slater (HFS) method are compared. Atomic charges, dipole moments, topological properties of the electron density distribution and polarizabilities, and first hyperpolarizabilities are calculated. Atomic charges obtained with the HFS method are found to be very close to those calculated with the MP2 method, from which we conclude that the HFS method describes to some extent electron correlation effects. Performing an MP2 calculation after an HF calculation improves the molecular dipole moments considerably, yielding values close to the experimental ones. HFS calculations are computationally less demanding than MP2 and yield comparable results for the electron density distributions, dipole moments and polarizabilities.     

A molecular mechanics study of the Si?O bond and alkyl-silanes

The standard MM2 force field and program have been modified to include Si? O groups, the force constants being derived from ab initio wavefunctions, and using partial atomic charges calculated from the empirical algorithm CHARGE2. Molecular mechanics calculations have been carried out on disiloxane, dimethoxy-dimethylsilane, methyl silyl ether, and cyclotrisiloxane, and reasonable agreement has been obtained between the observed and calculated geometries. In addition, the energies obtained using the modified force field have been tested against experimental data on alkyl silanes where energetic and structural information is available. Again good agreement is obtained. The application of the force field to extended Si? O systems will also be discussed.     

Conformational properties of polar polymers. I. Poly(vinyl chloride)

A recently developed method for including polar bonds in conformational energy calculations is applied to poly(vinyl chloride). Inductive effects on dipole moments and the effects of intervening atoms on electrostatic interaction energies are represented by polarizability centers in conjunction with bond centered dipoles. Solvation energies are estimated by means of a continuum dipole–quadrupole electrostatic model. Calculated energies of a number of conformations of meso and racemic 2,4-dichloropentane and the iso, syndio, and hetero forms of 2,4,6-trichloroheptane give satisfactory representations of isomer and conformer populations. Electrostatic effects are found to be quite important. However they appear to be effectively of sufficiently short range that the calculated conformer energies are found to be fit well by a linear combination of interaction parameters (consisting of gauche, skew chlorine, four-bond CH₂…CH₂, CH₂…Cl, and Cl…Cl interactions) conventional to vinyl polymers and a special four-bond interaction that arises when the bond sequence Cl? CH? CH²? CH? Cl is (nearly) coplanar. These interaction parameters when assembled into statistical weight matrices lead to calculated values of both the characteristic ratio and the dipole moment ratio in satisfactory agreement with experiment. Least energy paths for transitions between the most stable conformations are also calculated.     

Chlorosilanes: Development and application of MM2 force field parameters

The geometries, relative conformational energies, and dipole moments of mono and polychlorosilanes have been calculated using ab initio molecular orbital (MO) theory. Calculations at the HF/3–21G(*) level, with the exception of dipole moments, give reasonable agreement with experimental data. A new MM2 force field for chlorosilanes, which includes terms for bond length shortening and bond angle compression due to the attachment of electronegative Cl atoms, has been developed on the basis of experimental and ab initio results. The new force field is generally successful in predicting structural parameters, but is unable to reproduce the dipole moments of several model systems. While dipole moment predictions are not the authors' main interest, this failure defines a shortcoming in the MM2 method. The new parameters have been applied to problems in the prediction of stereochemistries of cyclic systems, and compared with experimental results where data are available.     

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.     

Experimental atomic charges from infrared intensities. Comparison with “ab initio” values

Atomic charges can be derived from observed infrared intensities and molecular dipole moments. The atomic charges so drived for a series of simple organic molecules are compared with atomic electron population data computed by quantum-mechanical calculations at various levels. It is shown that experimental charges agree very well with those computed by 6-31G^**.     

Molecular ion LiHe: ab initio study

High level ab initio calculations are performed on the molecular ion LiHe⁺. Potential energy curves for the low-lying singlet and triplet electronic states are calculated using the multi-reference configuration interaction and single-reference coupled cluster methods with large basis sets. The corresponding dipole moments and transition dipole moments functions are also determined. The basic spectroscopic properties and excitation energies of the electronic states are derived from rovibrational bound state calculations.