bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational Properties of 3‐Phenylpiperidine and 3‐Phenylpyrrolidine Opioid Analgesics
Authors: Froimowitz Mark
Published: January 2005

Conformational energy calculations have been performed on 3‐phenylpiperidine and 3‐phenylpyrrolidine opioids using the MM2 method. Phenyl equatorial conformers were found to be preferred for 1,2,3‐trimethyl‐3‐phenylpiperidines while phenyl axial conformers were preferred for the 2‐demethyl derivative and 1‐methyl‐3‐isobutyl‐3‐phenylpyrrolidine. These conformational differences may account for differences in their structure‐activity relationships. The geometries of these compounds were superimposed onto a rigid phenyl‐axial opioid with the result that the more active antipodes of alpha‐2,3‐dimethyl‐3‐phenylpiperidine and 3‐isobutyl‐3‐phenylpyrrolidine antagonists were found to be a better fit. However, for the beta derivative, which has not yet been resolved, the opposite antipode was found to be a better fit though the orientation of NH bond was quite different. There is a good agreement between the computed molecular geometries and those observed by x‐ray crystallography.
Rapid Location of the Preferred Interaction Sites between Small Polar Molecules and Macromolecules. I. Binding of Water to the Component Units of Nucleic Acids
Authors: Neto Marçal De Oliveira
Published: January 2005

An approximate procedure for the rapid detection of favored sites for the location of bound water on macromolecules has been developed with the aid of accurate electrostatic energy calculations. The method also enables us to picture the lability of the bound water molecules around the substrate. As an application the method has been used to study the interaction surface between nucleic acid components and a water molecule.
Rapid Location of the Preferred Interaction Sites between Small Polar Molecules and Macromolecules. II. Binding of Water to a Model Segment of B‐DNA
Authors: Neto Marçal De Oliveira
Published: January 2005

The procedure developed in Part I of this series is applied to the homopolymeric sequences poly(dA) · poly(dT) and poly(dG) · poly(dC) on the double helical structure of B‐DNA. Some aspects of the base sequence influence on the polymer's attraction for water molecule are described. The results are used to discuss the general hydration features of those systems in relation to recent experimental studies of DNA single crystals.
Nonempirical Atom‐Atom Potentials for Main Components of Intermolecular Interaction Energy
Authors: Sokalski W. A. , Lowrey A. H. , Roszak S. , Lewchenko V. , Blaisdell J. , Hariharan P. C. , Kaufman Joyce J.
Published: January 2005

Atom‐atom potentials representing separate contributions to the nonempirical interaction energy have been derived in the SCF decomposition scheme corrected for basis set superposition error by the counterpoise method. The nontransferable long‐range electrostatic multipole and classical induction terms have been evaluated directly from cumulative atomic multipole expansions, whereas the short‐range exchange, charge‐transfer, and electrostatic penetration contributions have been represented by simplified potentials of the form (β + δR−1) exp(−δR) fitted to the corresponding ab initio results for 336 dimer configurations formed by HF, H2O, NH3, CH4, CO, and CO2. The dominant anisotropic character of electrostatic multipole atom‐atom potentials and much more isotropic nature of the potentials representing short‐range terms is illustrated in the Appendix for head‐on interactions in CO ‥ OC and HF ‥ FH dimers.
A combined ab initio quantum mechanical and molecular mechanical method for carrying out simulations on complex molecular systems: Applications to the CH3Cl + Cl− exchange reaction and gas phase protonation of polyethers
Authors: Singh U. Chandra , Kollman Peter A.
Published: January 2005

We present an approach to couple ab initio quantum mechanical geometry optimiuzations with molecular mechanical optimizations, with the added capability to carry out molecular dynamics simulations of the systems to earch for new local minima. The approach is applied to the aqueous solution CH3Cl + Cl− exchange reaction and the gas phase protonation of polyethers.
Structural features of organic anions: 7‐Norbornadienyllithium
Authors: Lipkowitz Kenny , Burkett Anthony
Published: January 2005

The structure of 7‐norbornadienyllithium, a homoantiaromatic carbanion, is investigated with the semiempirical MNDO molecular orbital method. Alkene out‐of‐plane bendings persist even when the metal is fully solvated. The structural integrity of the monomer is retained in the dimer and solvated dimer; previously proposed dimers are inconsistent with lithium bonding and are not minimum energy structures on the MNDO hypersurface.
The role of d functions in ab initio calculations. II. The deformation densities of SO2, NO2, and their ions
Authors: Cruickshank D. W. J. , Eisenstein M.
Published: January 2005

Comparison of the optimized geometries and SCF energies for the series XO, XO2, XO, XO, with X = S,N shows that d(S) functions cause larger bond shortening and energy drop than d functions centered on first‐row atoms. This is further emphasized on comparing the separate effects of d(central atom) and d(O) functions for SO2 and NO, which are similar only for the first‐row molecule. The d(S) functions are also essential for proper prediction of the OSO angles. The deformation densities calculated for each series and the corresponding X–O shared populations, change as expected on adding electrons first into σ* then into π* molecular orbitals. In the regions around nuclei the deformation densities express the behavior of the atomic s and p valence orbitals or of their product inside their radial nodes. Introduction of d functions causes substantial polarization effects. For X = N these are mostly local except in the bonding regions where d(N) and d(O) functions are somewhat interchangeable. However, d(S) functions induce also unique changes in the deformation density near O. They cause π and π′ charge migration from O to S and a σ flow in the opposite direction. These effects are largest for the hypervalent species. The unique populations of the d(S) functions are much larger than those of d(N) and d(O) functions. The contribution of d(S) functions to bonding is related to the larger amplitude at small radii of the atomic 3d(S) orbital as compared with that of 3d(N). The difference in amplitudes is related to penetration effects. Diffuse p functions affect geometries and SCF energies of doubly, but not singly negative ions. However, they mostly describe the diffuse nonbonding clouds and do not affect bonding patterns.
Theoretical study of water‐pyridine complexes using intermolecular potentials
Authors: Genest Monique
Published: January 2005

Intermolecular potential functions have been used to determine the equilibrium structures of the water‐pyridine complexes. The dimer and symmetrical 2:1 water pyridine systems have been studied. Three water models, ST2, TIPS2, and EMPWI have been combined with two different Lennard Jones nonbonded parameters and various charge distributions for the pyridine molecule to describe the systems. For the dimer, results show two distinguishable classes of preferential hydration sites, which are specific sites corresponding to hydrogen‐bonded dimer and nonspecific sites located near the hydrophobic regions. Calculations performed on hydrogen‐bonded symmetrical complexes show that the planar complex is generally less stable than the complex with water molecules perpendicular to the pyridine plane. For these complexes, the major factor that influences the hydrogen‐bonded configurations is the choice of the water model. The importance of atomic charge distributions for the solute over the choice of potential parameters is pointed out. Finally, the effective lone pair representation on the aromatic nitrogen atom is shown to improve the hydrogen bond geometry and the stability of the complexes.
Polarization counterpoise corrections to correlated hydrogen bond interaction energies
Authors: Loushin Sharilyn K. , Dykstra Clifford E.
Published: January 2005

Basis set superposition error in hydrogen‐bonded systems can exaggerate attraction calculated from self‐consistent field energies as well as from electron correlation energies. One cause of this error is the basis set deficiency in describing the charge polarization of one constituent molecule when its bonding partner approaches. That constituent molecule's description is improved partly because of the proximity of the partner's basis functions, independent of real attraction. That polarization‐related error is shown to occur primarily at the SCF level and not at correlated levels.
Ab initio calculations on the effect of polarization functions on disiloxane
Authors: Grigoras Stelian , Lane Thomas H.
Published: January 2005

The effect of polarization functions for ab initio molecular orbital calculations at the 3‐21G* level has been studied for disiloxane. Calculated molecular geometry, dipole moment, and the linearization barrier variation were analyzed for different uncontracted polarization functions. It was concluded that variation of the polarization function on oxygen has only a minor influence on the molecular properties of disiloxane, but its presence is required to obtain a bent geometry for the disiloxane bond. The calculated molecular properties of disiloxane are greatly influenced when the polarization function on silicon is varied. Two different values (0.3 and 0.9) for the exponent of the silicon polarization function provide results comparable to the experimental values for disiloxane. The only significant differences between the results obtained from ab initio calculations using the two polarization functions are in net atomic charges. The uncontracted polarization function of silicon with a value of 0.3 for its exponent is transferable to other organosilicon compounds. Calculated molecular geometries of flexible or rigid structures are in very good agreement with the experimental values.
Transition structure in a diabatic surface formalism
Authors: Bernardi Fernando , McDouall Joseph J.W. , Robb Michael A.
Published: January 2005

The theory of an implementation of the diabatic surface model within the Heitler–London valence bond approach is described. It is shown that the HL–VB wave function can be obtained from a Van‐Vleck transformation of an MC–SCF wave function which has been built from atom‐localized orbitals. This wave function is built from a superposition of two diabatic components, reactantlike and productlike. The transition structure is then obtained as the minimum of the seam of intersection of the diabatic surfaces and the algorithm for performing this constrained optimization is described. Several areas of application are also discussed.
Analysis of the π‐electronic structure of infinitely large networks. I. Some remarks on the characteristic polynomial and density of states of large polycyclic aromatic hydrocarbons
Authors: Hosoya Haruo , Aida Misako , Kumagai Reiko , Watanabe Kazu
Published: January 2005

General expressions of the characteristic polynomials of various series of cyclic and linear polymers of polycyclic aromatic hydrocarbons are presented, i.e., polyacene, zigzag‐polyacene, 1,4‐dimethylbenzene polymer, polyperylene, etc. The densities of states of cyclic and linear polymers with the same repetitive units are shown. In some cases the allowed region of the energy levels of these polymers is found not to be the same. Several related problems are discussed.
The density amplitude ρ½ and the potential which generates it
Authors: March N. H.
Published: January 2005

The square root of the density ρ½ satisfies a Schrödinger equation with an effective local potential 𝒱(r). The form of this potential is obtained for (a) the ground state of the Be atom, (b) neutral atoms in the limit of very large atomic number from the statistical theory, and (c) almost spherical molecules XH4, again in the limit of many electrons. Some comments are made on the possibility of relativistic generalization of this method.
PERTURB: A special‐purpose algebraic manipulation program for classical perturbation theory
Authors: Fried Laurence E. , Ezra Gregory S.
Published: January 2005

Classical perturbation theory provides a particularly promising route to EBK quantization of nonseparable systems. However, the number of terms generated when implementing perturbation theory for systems with more than two degrees of freedom can prove too large for general purpose symbolic manipulators to handle. We describe PERTURB, a specialized algebraic manipulation program written in C for quantization of multidimensional systems. A review of operator based classical perturbation theory is given, and the relationship between this type of perturbation theory and quantum mechanical Van Vleck perturbation theory discussed. The relative performance of the Dragt–Finn and Lie transform algorithms is assessed.
The shape of molecular charge distributions: Group theory without symmetry
Authors: Mezey Paul G.
Published: January 2005

A group theoretical framework is proposed for a detailed characterization of the shapes of electronic charge distributions of general, asymmetric molecules. The proposed shape groups are the homology and cohomology groups of charge density contour surfaces. These shape groups depend on two real parameters, the charge density value a for the contour and a curvature parameter b. The two‐parameter family of various homology groups and cohomology groups of charge density contour surfaces is independent of the symmetry properties of the molecules and gives a concise description of the dominant shape characteristics. For any fixed parameter value b these groups may change only at specific charge density values, characteristic to the given molecule. On the other hand, for a fixed‐charge density contour the group changes induced by a change in the curvature parameter b provide a description of the fine details of the shape of the electron density. The changes in the structure of these groups follow strict algebraic relations, that provide a quantitative measure for shape‐similarity between various molecules. The two‐parameter shape group method is an extension of an earlier method proposed for biochemical applications.
Stereotopological indices for a family of chemical graphs
Authors: Millett Kenneth C.
Published: January 2005

We describe a mathematical method that can be employed to define stereotopological indices of placements of certain graphs in space. These indices are applied to successfully distinguish between configurations in a chemically interesting family of knotted and/or linked four‐valent oriented graphs in space. The methods are fundamentally algebraic and combinatorial in nature and are most readily understood in the context of calculations and the study of several key examples that are presented.
Molecular orbital theory of the properties of inorganic and organometallic compounds 5. Extended basis sets for first‐row transition metals
Authors: Dobbs K. D. , Hehre W. J.
Published: January 2005

A series of efficient split‐valence basis sets for first‐row transition metals, termed 3‐21G, has been constructed based on previously‐formulated minimal expansions of Huzinaga, in which each atomic orbital has been represented by a sum of three gaussians. The original Huzinaga expansions for s‐ and p‐type orbitals (except those for 1s) have been fit by least squares to new three‐gaussian combinations in which the two sets of orbitals (of the samenquantum number) share gaussian exponents. The Huzinaga three‐gaussian expansions for ls and 3d atomic orbitals have been employed without alteration. The valence description of the 3‐21G basis sets comprises 3d‐, 4s‐ and 4p‐type functions, each of which has been split into two‐ and one‐gaussian parts. 4p functions, while not populated in the ground state of the free atoms, are believed to be important to the description of the bonding in molecules. The performance of the 3‐21G basis sets is examined with regard to the calculation of equilibrium geometries and normalmode vibrational frequencies for a variety of inorganic and organometallic compounds containing first‐row transition metals. Calculated equilibrium structures, while generally superior to those obtained at STO‐3G, are not as good as those for compounds containing main‐group elements only. The calculations generally underestimate the lengths of double bonds between transition metals and main‐group elements, and overestimate the lengths of single linkages. Calculated normal‐mode vibrational frequencies for metal‐containing systems are less uniform than in those for main‐group compounds.
Voronoi binding site models
Authors: Crippen Gordon M.
Published: January 2005

A frequently occurring problem in drug design and enzymology is that the binding constants for several compounds to the same site are known, but the geometry and energetic interactions of the site are not. This paper presents in detail a novel approach to the problem which accurately but compactly represents the allowed conformation space of each ligand, accurately depicts their three‐dimensional structures, and realistically allows each ligand to adopt the conformation and positioning in the site which is most favorable energetically. The investigator supplies only the ligand structures and observed binding free energies, along with a proposed site geometry. With no further assumptions about how the ligands bind and what parts of the ligands are important in determining the binding, the algorithm fits the observed binding energies without leaving outliers, predicts exactly how each of the given ligands binds in the site, and predicts the strength and mode of binding of new compounds, regardless of chemical similarity to the original set of ligands. The method is illustrated by devising a simple site that accounts for the binding of five polychlorinated biphenyls to thyroxine binding prealbumin. This model then predicts the binding energies correctly for an additional six biphenyls, and fails on one compound.
Determination of an empirical energy function for protein conformational analysis by energy embedding
Authors: Crippen Gordon M. , Ponnuswamy P. K.
Published: January 2005

It is quite easy to propose an empirical potential for conformational analysis such that given crystal structures lie near local minima. What is much more difficult, is to devise a function such that the native structure lies near a relatively deep local minimum, at least in some neighborhood of the native in conformation space. An algorithm is presented for finding such a potential acting on proteins where each amino acid residue is represented by a single point. When the given structure is either an α‐helical, β‐strand, or hairpin bend segment of pancreatic trypsin inhibitor, the resulting potential function in each case possesses a deep minimum within 0.10 Å of the native conformation. The improved energy embedding algorithm locates a marginally better minimum in each case only 0.1–1.3 Å away from the respective native state. In other words, this potential function guides a conformational search toward structures very close to the native over a wide range of conformation space.
An evaluation of the performance of diffuse function‐augmented basis sets for second row elements, Na‐Cl
Authors: Spitznagel Günther W. , Clark Timothy , von Ragué Schleyer Paul , Hehre Warren J.
Published: January 2005

The energetic effects of the addition of diffuse functions to molecules with second‐row elements are much less dramatic than those for their first‐row counterparts. Although diffuse functions on second‐row elements have little effect on the geometries and vibrational frequencies of neutral molecules, significant changes are found for anions. While the largest basis set, 6‐31 + G*, generally performs best, the results at 3‐21 + G* are comparable, and this basis can be recommended for practical applications.
The Hylleraas‐CI method in molecular calculations: Two‐electron integrals
Authors: Largo‐Cabrerizo A. , Clementi E.
Published: January 2005

In the Hylleraas‐CI method, first proposed by Sims and Hagstrom, correlation factors of the type r are included into the configurations of a CI expansion. The computation of the matrix elements requires the evaluation of different two‐, three‐, and four‐electron integrals. In this article we present formulas for the two‐electron integrals over Cartesian Gaussian functions, the most used basis functions in molecular calculations. Most of the integrals have been calculated analytically in closed form (some of them in terms of the incomplete Gamma function), but in one case a numerical integration is required, although the interval for the integration is finite and the integrand well‐behaved. We have also reported on partial and preliminary computations for the H2 molecule using our four‐center general formulas; a basis set of s‐ and p‐type functions yielded at R = 1.4001 Å an energy of ‐ 1.174380 a.u. to be compared with Kolos and Wolniewicz value of ‐ 1.174475.
Application of SINDO1 to phosphorus compounds
Authors: Jug Karl , Schulz Joachim
Published: January 2005

SINDO1 calculations are presented for ground state geometries, heats of formation, ionization potentials and dipole moments. These calculations are based on a new parametrization of SINDO1 for second‐row elements which features inclusion of 3d orbitals and zero point energies. The comparison shows an improvement over MNDO, especially for hypervalent phosphorus compounds.
Atomic physicochemical parameters for three dimensional structure directed quantitative structure‐activity relationships III: Modeling hydrophobic interactions
Authors: Ghose Arup K. , Pritchett Avis , Crippen Gordon M.
Published: January 2005

In an earlier article8 the need was demonstrated for atomic physicochemical properties for three dimensional structure directed quantitative structure‐activity relationships, and it was shown how atomic parameters can be developed for successfully evaluating the molecular octanol‐water partition coefficient, which is a measure of hydrophobicity. In this work we report more refined atomic values of octanol‐water partition coefficients derived from nearly twice the number of compounds. Carbon, hydrogen, oxygen, nitrogen, sulfur and halogens are divided into 110 atom types of which 94 atomic values are evaluated from 830 molecules by least squares. These values gave a standard deviation of 0.470 and a correlation coefficient of 0.931. These parameters predicted the octanol‐water partition coefficient of 125 compounds with a standard deviation of 0.520 and a correlation coefficient of 0.870. There is only a correlation coefficient of 0.432 between the atomic octanol‐water partition coefficients and the atomic contributions to molar refractivity over the 93 atom types used for both the properties. This suggests that both parameters can be used simultaneously to model intermolecular interactions. We evaluated the CNDO/2 gross atomic charge distribution over several molecules to check the validity of our classification. We found that the charge density on the heteroatoms in conjugated systems is strongly affected by the presence of similar atoms in the conjugation which suggests it should be incorporated as a separate parameter in evaluating the partition coefficient.
The dynamic “level shift” method for improving the convergence of the SCF procedure
Authors: Mitin A. V.
Published: January 2005

This article is concerned with the improvement of convergence of the iterative procedure for solving the Hartree–Fock–Roothaan equations by the dynamic “level shift” method.
Integral data compression for FPS 64‐BIT processors: Improved I/O and reduced storage
Authors: Hurst G. J. B. , Dupuis M.
Published: January 2005

Compression of two‐electron integral data is used to reduce integral storage and I/O requirements with FPS M64 Series (formerly FPS‐X64) processors. Schemes are developed and implemented in assembly language to compress floating‐point values to a fixed‐point accuracy, and unsigned integer numbers. The floating‐point scheme stores only the significant bits of the mantissa and a short, biased exponent. The unsigned integers are packed into fixed‐length fields just long enough to hold the largest value. The packing procedures are tested on FPS‐164 and FPS‐264 processors (since renamed M64/145 and M64/60 by FPS) and incorporated into HONDO to compress two‐electron integral files. Reduction factors of 0.2–0.4 are obtained for floating‐point compression and 0.3–0.5 for index packing, with typical overall factors around one‐third. The advantages of improved I/O and storage efficiency are accompanied by a small increase in processor time to perform the packing and unpacking. Timing changes for HONDO are presented, and both packing schemes dramatically reduce SCF elapsed times with FPS‐264 processors. It is concluded that compression effectively extends external storage capacities, improves I/O efficiency, and can reduce the elapsed time of I/O bound calculations.
Improved algorithm for the calculation of one‐electron two‐center integrals with STOs
Authors: Rico J. Fernández , López R. , Ramírez G.
Published: January 2005

In a previous article (J. Fernández Rico, R. López and G. Ramírez, J. Comp. Chem., 9, 790 (1988)) we have proposed the calculation of molecular integrals involving STOs by means of some recurrence relations which use two sets (h and H) of overlap integrals (basic matrices). In the present paper, we derive explicit expressions of these integrals employing the two‐range expansion of the 0s‐function. This approach yields equations for the elements of the two basic matrices in terms of two further matrices, k(x,y) and i(x,y), and some auxiliary functions. Relations between the elements of these matrices and the functions are thoroughly explored and numerical tests are included for illustrating the behavior of the method.
Linearized embedding: A new metric matrix algorithm for calculating molecular conformations subject to geometric constraints
Authors: Crippen Gordon M.
Published: January 2005

There are many methods in the literature for calculating conformations of a molecule subject to geometric constraints, such as those derived from two‐dimensional NMR experiments. One of the most general ones is the EMBED algorithm, based on distance geometry, where all constraints except chirality are converted into upper and lower bounds on interatomic distances. Here we propose a variation on this where the molecule is assumed to have fixed bond lengths, vicinal bond angles and chiral centers; and these holonomic constraints are enforced separately from the experimental constraints by being built into the mathematical structure of the problem. The advantages of this approach are: (1) for molecules having large rigid groups of atoms, there are substantially fewer variables in the problem than all the atomic coordinates; (2) rigid groups achieve in the end more accurate local geometry (e.g., planar aromatic rings are truly planar, chiral centers always have their correct absolute chirality); (3) it is easier to detect inconsistencies between the holonomic and the experimental constraints; and (4) when generating a random sampling of conformers consistent with all constraints, the probability of achieving satisfactory structures tends to be greater.
Molecular mechanics of peroxides. II. Cyclic compounds
Authors: Carballeira L. , Mosquera R. A. , Rios M. A.
Published: January 2005

The conformations of various cyclic peroxides have been determined using a molecular mechanics force field developed by the authors and previously applied to linear peroxides. Comparison of the results with those of experimental and ab initio studies shows that this force field may be employed without correction for cyclic compounds.
A data compression method applicable to first‐order convergent iterative procedures
Authors: Shepard Ron
Published: January 2005

A data compression method is presented that is generally applicable to first‐order convergent iterative procedures that employ subspace expansions or extrapolations based on successive correction vectors. This method is based on the truncation of insignificant information in successive correction vectors. Although the correction vectors themselves may be severely truncated with the proposed approach, the final solution vector may be represented to arbitrary accuracy. A feature of the proposed method is that more slowly convergent iterative procedures allow the correction vectors to be more severely truncated without affecting the overall convergence rate. The method is implemented and applied to the iterative Davidson diagonalization method. If the compressed representation of the expansion vectors can be held in main computer memory, then a significant reduction in the I/O requirements is achieved.
An empirically adjusted Newton–Raphson algorithm for finding local minima on molecular potential energy surfaces
Authors: Stanton John F. , Bernholdt David E.
Published: January 2005

A simple extension of the Newton–Raphson method is proposed that approximately accounts for anharmonicity in bond‐stretching coordinates. By modeling each bonded distance in a polyatomic molecule as a Morse oscillator with no anharmonic stretch‐stretch or stretch‐bend coupling, a multiplicative correction factor to the Newton–Raphson step is derived. Representative examples suggest that the rate of convergence of the proposed scheme is typically faster than that of the standard Newton–Raphson method.
Semiempirical AM1 electrostatic potentials and AM1 electrostatic potential derived charges: A comparison with ab initio values
Authors: Ferenczy Gyorgy G. , Reynolds Christopher A. , Richards W. Graham
Published: January 2005

Electrostatic potentials calculated from AM1 wave functions have been compared with ab initio STO‐3G values and qualitative agreement has been found. Atomic charges derived from AM1 electrostatic potentials for both experimental and AM1 optimized geometries are of comparable quality with STO‐3G potential derived charges. These results suggest that the AM1 electrostatic potential may be useful both in its own right and also for deriving atomic charges for use in molecular dynamics studies.
Numerical solution of a partial differential equation system describing chemical kinetics and diffusion in a cell with the aid of compartmentalization
Authors: Salzner U. , Otto P. , Ladik J.
Published: January 2005

To build a kinetic model of a cell with diffusion one has to solve a coupled nonlinear partial differential equation system consisting of several hundred equations. (Several hundred chemical components undergoing several hundred reactions.) To solve this formidable mathematical problem the division of the model cell into compartments (most biochemical reactions take place in a certain part of the cell) was suggested.1 Solving the differential equation system in one compartment, the results can be used as input at other compartments until mutually consistent solutions are achieved.

To test this suggestion 10 coupled chemical reactions with diffusion were investigated in a model that contains three compartments. The results in the case of pure diffusion are in excellent agreement with and without compartmentalization. After this the full problem was treated by compartmentalization using for the solution of the differential equation system a discretization of the concentrations as functions of space and time and the Newton–Raphson iterative procedure. The results obtained give reasonable space and time dependence for the concentrations of all 10 components.
Relaxed potential energy surfaces of N‐linked oligosaccharides: The mannose‐α(1 → 3)‐mannose case
Authors: Imberty Anne , Tran Vinh , Pérez Serge
Published: January 2005

We report calculations of potential energy surfaces where all the internal coordinates of the disaccharide Man‐α(1 → 3)‐Man‐α‐O‐Me were relaxed and minimized through an extensive molecular mechanics scheme. Flexibility within the mannopyranose rings plays a crucial role. Introduction of the relaxed principle into the conformational description of the disaccharide does not greatly alter the overall shape of the low‐energy domains but it reveals new local minima. However, its principle effect is the lowering of energy barriers in the potential energy surface. New conformational transitions about the glycosidic bonds appear, permiting pathways among the low energy sections. This occurs with only little variation of the classical 4C1 conformation of the mannopyranose residues. All the conformations observed in the solid state, along with those already predicted through the joint use of NMR and modeling techniques, fall into the populations of stable conformers calculated in the present work. Moreover, a satisfactory agreement is reached between previously observed NOE values, and the theoretical one, calculated from the averaging of more than 500 microstates. The present results reconciliate most of the apparently conflicting data previously reported; they provide strong support for the application of the concept of conformational averaging to solution behavior. Some limitations of the proposed methodology are also discussed.
On the enumeration and generation of polyhex hydrocarbons
Authors: Müller W. R. , Szymanski K. , Knop J. V. , Nikolić S. , Trinajstić N.
Published: January 2005

A novel efficient computer‐oriented approach, based on the DAST (dualist angle‐restricted spanning tree) code, is introduced for enumeration and generation of planar polyhex hydrocarbons. It is much faster than other approaches in the literature. The numbers of planar polyhex hydrocarbons with 14 hexagons are reported for the first time.
Effects of computational variations for determining binding energies of diastereomeric complexes when using MM2
Authors: Still Miron G. , Rogers L. B.
Published: January 2005

Variations of a procedure have been examined for minimization of the energies, calculated using MM2, of two docked molecules. After doing the intramolecular minimization of the individual molecules, randomized orientations of the rigid molecules were brought together to form complexes and the nonbonded energies of interaction were then minimized. Next, pairs having energies within 4.0 kcal/mol of the most stable pair were minimized further by atom‐by‐atom relaxation of the complex. Only two repetitions of the last two steps were found to give values within 0.001 kcal/mol in more than 90% of the cases. Compared to two other variations of the procedure, this method appeared to avoid erroneous (local, not global) minima. Finally, this overall procedure was tested against chromatographic data in the literature. Using only the most stable comformer of each species, the results appeared to be in qualitative agreement with fractionation data for enantiomeric aminoethanes on a chiral packing very similar to the one modeled here.
Coordination numbers for biomolecular hydration: A quantitative method based on pattern recognition analysis of Monte Carlo simulations of aqueous solutions
Authors: Marchese Francis T.
Published: January 2005

A coordination number model (CNM) has been developed that reproduces coordination numbers generated by rigorous Monte Carlo simulations of dilute aqueous solutions. The molecular coordination number is calculated by using the volume of the Voronoi polyhedron surrounding each solute atom and a set of linear least squares fitted parameters. Agreement with simulation data is good, with average deviation of less than 5%. Although CNM is presently parameterized against a simulation database founded on the potential functions of Clementi and coworkers, the method is perfectly general and can be applied to simulation data derived from any potential function form. Finally, the method is fast and can predict coordination numbers within minutes on a microcomputer.
Diazonium ions. Topological electron density analysis of cyclopropeniumyldiazonium dications and of their stability toward dediazoniation
Authors: Glaser Rainer
Published: January 2005

Results are presented of topological analyses of the electron density functions of cyclopropeniumyldiazonium dication, 1, of its 2,3‐diamino derivative, 2, and of their products 3 and 4, respectively, formed by dediazoniative ring‐opening. The new CN‐bonding type in 1 and 2, recently realized synthetically in derivatives of 2, is compared to prototypical aliphatic diazonium ions with regard to electronic structure and thermodynamic stability, factors that both are crucial for the appreciation of the mechanisms of deamination reactions of chemical and biochemical significance. Association of the dication with N2 involves density accumulation in the CN bonding region, occurs without major overall charge transfer, and leads to an electrostatically favorable quadrupolar charge distribution in the diazonium ion. The CN‐bonding model recently proposed for aliphatic diazonium ions also applies to these dications. 1 is thermodynamically stable while the dediazoniation of 2 is exothermic but kinetically hindered. Our best estimates for the reaction energies of the dediazoniations 1 → 3 + N2 and 2 → 4 + N2, respectively, are 65.5 and −7.2 kcal/mol, respectively. We have found that, in general, the cation is destabilized and that N2 is stabilized upon CN‐bond cleavage. Cations force N2 to form diazonium ions. The remarkable difference between the stabilities of 1 and 2 is primarily due to the larger destabilization of the open dication 3 compared to 4. Push‐pull interactions between the diazo‐ and the overall electron‐withdrawing amino‐functions characterize the electronic structure of 2. CN‐Bonding and the overall electronic structure of 2 are incompatible with the usual Lewis resonance notations. Instead of dismissing the Lewis notations, it is shown that the topological description can be reconciled with the Lewis notations if the resonance forms are interpreted in a way that appropriately reflects the atom populations and first moments. Implications of the model with regard to reactivity are discussed.
Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and ab initio study of hydride‐ion transfer between the NADH analogue, 1‐methyl‐dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase
Authors: Cummins Peter L. , Gready Jill E.
Published: January 2005

As part of a study of factors controlling biological redox reactions of nicotinamide cofactors [nicotinamide adenine dinucleotide (phosphate) NAD(P)H], we have investigated the effect on a model reaction of the conformational state (cis or trans) of the carboxamide side chain, using quantum chemical methods. The reaction is that for the enzyme dihydrofolate reductase between the NADPH analogue, 1‐methyl‐dihydronicotinamide, and the protonated forms of the folate and dihydrofolate substrate analogues, pyrazine and dihydropyrazine. Some calculations on pterin and dihydropterin substrate analogues were also carried out in order to gauge the effects of inter‐ring coupling. The influence of carboxamide side‐chain conformation of nicotinamide on the energetics of the hydride‐ion transfer, and on the structures of the transition states and stable intermolecular‐interaction complexes, are examined as a function of the orientation of approach of the reactants. These approach geometries include those corresponding to the observed binding of cofactor and either substrate or inhibitor in the enzyme active site. Reactant, product, reactants‐complex, and transition‐state geometries were optimized at the semiempirical AM1 level, while ab initio SCF/STO‐3G and SCF/3‐21G single‐point calculations were carried out at the AM1 optimized geometries for all species, as well as full geometry optimizations for isolated reactants and products. The results show that reactants‐complex and transition‐state energies are lower for the trans conformer of dihydronicotinamide than for the cis conformer, due to more favorable H‐bonding or electrostatic interactions with the protonated substrate. Also, consideration of the structural parameters, including reaction coordinate bond lengths, ring geometries, and charge distributions, indicate that the trans transition states are more product‐like than those for the cis. For the (trans) approaches corresponding to the enzymic orientation for substrate, the intermolecular interaction for the folate reaction lacks the stabilizing influence of the formal H‐bond which is present for the dihydrofolate reaction, and consequently the reactants‐complex and transition state are less stable.
ARGOS, a vectorized general molecular dynamics program
Authors: Straatsma T. P. , McCammon J. A.
Published: January 2005

The organization of the highly vectorizable molecular dynamics simulation program ARGOS is described. The specific choice of the data structure and the separation of the calculation of interactions involving solutes and solvent molecules allows a considerable improvement in computation speed. Illustrative results are given for the NEC SX‐2/400 supercomputer. For the simulation of a large biological molecule in water a speedup factor of 5 is obtained as a result of vectorization of the code to 87%. The parts of the code used in a simulation of pure water could be vectorized to 98%, leading to an overall speedup factor due to vectorization of 13. The simulation of pure water runs over 300 times faster on the SX‐2/400 than on the VAX 8650.
Molecular mechanics parameterization: Bond lengths and angles for nitrogen and phosphorus containing compounds
Authors: Leonard Joseph M. , Ashman William P.
Published: January 2005

Molecular mechanics provides an excellent means of generating reasonable chemical structures in a short amount of time. Using a classical representation, a molecule can be partitioned into a collection of n‐fold atomic interactions, each with an associated force constant. In order for a calculation to proceed, all of the required force constants must be known. This article presents a method of rapidly determining the values for missing parameters using appropriately scaled quantum chemical techniques.
AM1 study of acid‐catalyzed hydrolysis of maleamic (4‐amino‐4‐oxo‐2‐butenoic) acids
Authors: Katagi Toshiyuki
Published: January 2005

The acid‐catalyzed hydrolysis mechanisms of maleamic (4‐amino‐4‐oxo‐2‐butenoic) acids were studied using AM1 method. The reaction proceeded mainly in two steps: (1) nucleophilic attack of the undissociated carboxyl group on the adjacent aminocarbonyl carbon via a zwitterionic intermediate; and (2) the rate‐determining proton transfer to form the zwitterionic tetrahedral intermediate. In each step, the hydration of water and hydronium ion molecules was important in stabilizing the polarized intermediates. The substituent effects at the amide moiety and the 2,3‐positions of the maleamic acids were qualitatively estimated for each step.
An improved empirical force field for saturated hydrocarbons
Authors: Dillen Jan L. M.
Published: January 2005

A new molecular mechanics force field for alkanes is presented. The force field aims to eliminate some identified failures of the well‐known MM2 force field. The new energy function gives an improved prediction of the rotational barriers of highly congested molecules, a better calculation of short nonbonded contacts, and the correct reproduction of bond elongation in small torsion angles. The calculation of sublimation enthalpies is also improved. The standard deviation of the formation enthalpies for a set of 54 compounds is 0.63 kcal/mol; this compares with the reported value of 0.42 calculated with MM2 and MM3 for different sets. The force field parameters were obtained using a least squares method.
Construction and molecular modeling of phospholipid surfaces
Authors: Charifson Paul S. , Hiskey Richard G. , Pedersen Lee G.
Published: January 2005

A protocol is given for the construction of phospholipid surfaces that possess variable head groups and thus variable net charge. Ab initio quantum mechanical calculations are performed to establish the necessary force field (AMBER) parameters. The charge distribution is defined by an electrostatic potential method consistent with the ab initio wave function. As a model calculation, a monolayer surface with head groups of phosphatidylserine and phosphatidylcholine derived from the crystal structure of 1,2‐dilauroyl‐DL‐phosphatidylethanolamine (DLPE) is placed in a water bath with two Ca(II) ions present. The resultant surface is energy‐optimized followed by 64 ps of molecular dynamics integration. Evaluation of calcium ion coordination environments, characterization of the P‐N dipole inclination with respect ot the plane of the monolayer, and calculation of molecular surface area is performed and compared with experimental data.
Minimization and molecular dynamics studies of guanosine and Z‐DNA modified by N‐2‐acetylaminofluorene
Authors: Fritsch V. , Westhof E.
Published: January 2005

The modeling program AMBER 3.0 was used to study the conformations adopted by the C8‐substituted guanosine adduct of the carcinogen N‐2‐acetylaminofluorene (AAF), called dGuo‐AAF. This conformational study was extended to the hexamer d(CGCGCG)2 in the Z form, modified by AAF at guanine G4 with the carcinogen situated at the helix exterior in two different orientations (named ZAAF‐5′ and ZAAF‐3′). Considering the importance of electrostatic interactions in case of charged molecules like nucleic acids, minimization and molecular dynamics (MD) were performed using different electrostatic parameters (dielectric functions and scale factors). For that purpose, a subroutine allowing the use of a sigmoidal distance‐dependent dielectric function εcal has been added to the program. For dGuo‐AAF, the results show a great importance of the starting conformation and of the force field parameters on the minimization and MD behaviors. For the AAF‐modified Z‐DNA, the results display a pronouned dependence on the choice of the set of electrostatic parameters as well. With the distance‐dependent dielectric function ε = r, the force field parameters favor the formation of intramolecular H bonds, which can lead to important distortions of Z‐DNA. The use of ε = 4r or ε = εcal attenuates effectively such a tendency, except in full MD simulations. The dielectric function εcal is computing intense, but often similar results are obtained with ε = 4r, especially with the use of the BELLY option. AAF appears to prefer the ZAAF‐5′ conformation, i.e., with the fluorene ring stacking on the sugar phosphate backbone of the following 5′ C‐G bases. Such a conformation is further stabilized by an intramolecular hydrogen bond between the amino group of the 3′ cytosine and the carbonyl group of AAF. The fluorene ring, although mobile around its long axis, does not flip‐flop between its two main orientations, ZAAF‐5′ and ZAAF‐3′. The presence of the AAF does not prevent the ZI to ZII transitions. Whatever the electrostatic parameters, the presence or absence of AAF, the cytosine sugars stay in the C2′‐endo pucker domain. In unmodified Z‐DNA, the guanine sugars stay in the C3′‐endo region, except for the terminal guanines which transit to the C2′endo region. In modified Z‐DNA, the sugar of the modified guanine behaves as a terminal guanine sugar.