bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular conformations from distance matrices
Authors: Glunt W. , Hayden T.L. , Raydan M.
Published: January 2005

Two algorithms are introduced that show exceptional promise in finding molecular conformations using distance geometry on nuclear magnetic resonance data. The first algorithm is a gradient version of the majorization algorithm from multidimensional scaling. The main contribution is a large decrease in CPU time. The second algorithm is an iterative algorithm between possible conformations obtained from the first algorithm and permissible data points near the configuration. These ideas are similar to alternating least squares or alternating projections on convex sets. The iterations significantly improve the conformation from the first algorithm when applied to the small peptide E. coli STh enterotoxin. © 1993 John Wiley & Sons, Inc.
Conformational analysis of bradykinin by annealed molecular dynamics and comparison to NMR‐derived conformations
Authors: Salvino Joseph M. , Seoane Peter R. , Dolle Roland E.
Published: January 2005

Conformational analysis of bradykinin (BK), a nonapeptide of the sequence RPPGFSPFR, was accomplished using annealed molecular dynamics (AMD) at 1000 K in BIOGRAF 2.2. One hundred anneal cycles produced 100 conformations over approximately 2000 ps. These conformations were compared to structures derived by nuclear magnetic resonance (NMR) methods for similar shape and energy. Energy minimization of relevant conformations using both BIOGRAF 2.2 and AMBER 3.0a revealed that the AMD‐determined conformations are in the same energy range as the NMR‐determined structures. Also, the shape of the relevant conformations appeared similar, suggesting that AMD is a good tool for the conformational analysis of small peptide ligands. © 1993 John Wiley & Sons, Inc.
Improved solutions to the one‐center McMurchie—Davidson tree search problem
Authors: Cisneros Gerardo
Published: January 2005

We present an improvement to Johnson, Gill, and Pople's results for reducing the cost of using the McMurchie–Davidson RNLM recurrence relation for one‐center integrals. Recursive replacement of singly referenced and single‐term auxiliary integrals results in floating point operation (FLOP) savings of up to 11% and explicit auxiliary integral calculation reductions of up to 76% with respect to the full list and up to 46% with respect to FLOP‐reduced lists with no replacement. The programs are written in the string‐manipulation language Convert; one of the programs automatically generates a FORTRAN subroutine given an integral list. © 1993 John Wiley & Sons, Inc.
Theoretical comparison of conformational properties of molecules: Conformational probability maps and similarity index
Authors: Bagińki Maciej , Piela Lucjan
Published: January 2005

The conformational analysis for a molecule is often performed by assuming that the total conformational energy is a function of two dihedral angles. The resulting conformational energy map is sometimes not easy to interpret because what counts is not energy differences but rather the probability distribution map at a given temperature. In the present article, an algorithm to calculate such a map is given. An example concerning N‐substituted amino sugars shows how the conformational probability map may be interpreted. In addition, a similarity index is proposed to get a measure of similarity of the conformational properties of two molecules. The index is based upon the analysis of the conformational probability maps for both molecules. © 1993 John Wiley & Sons, Inc.
Conformational analysis of 2,3,6,7‐tetrahydroazepines with implications for D1‐selective benzazepines
Authors: Alkorta Ibon , Villar Hugo O. , Cachau Raul E.
Published: January 2005

A conformational study of the 2,3,6,7‐tetrahydroazepine (THA) and closely related systems has been carried out using MM3 and CHARMm molecular mechanics, AM1 semiempirical, as well as Hartree‐Fock and local density functional (LDF) ab initio methods. For THA, all methods give similar optimal geometries; however, only MM3 agrees with the Hartree‐Fock calculations using a 6‐31G* basis set and LDF in the rank order of energies and nature of the stationary points characterized. AM1 shows serious disagreements with those results. Tetrahydrobenzazepines and a D1 receptor agonist containing the THA nucleus were studied using CHARMm, MM3, and AM1 calculations. All methods provide similar descriptions of the geometries of the conformations accessible to these compounds. However, the same disparities in the rank order of energies are observed. © 1993 John Wiley & Sons, Inc.
Molecular interaction potential: A new tool for the theoretical study of molecular reactivity
Authors: Orozco Modesto , Luque F.J.
Published: January 2005

A new methodology to compute molecular interaction potentials (MIPs) is developed and tested. The calculation of the MIP is based upon the generalization of the rigorous quantum mechanical molecular electrostatic potential (MEP) and further addition of a classical repulsion‐dispersion term. As a result, the MIP is able to represent not only with high accuracy electrostatic interactions but also represent in a suitable way steric effects. The analysis of the results obtained for different molecules demonstrates the superiority of the MIP with regard to the standard MEP to describe nonbonded interactions, in particular hydrogen bonds. The comparison of results calculated at the ab initio I 6‐31G* and semiempirical AM1 levels points out the suitability of semiempirical calculations to qualitatively reproduce the most relevant reactive features of the molecules. Finally, possible applications of the MIP in different fields are discussed. © 1993 John Wiley & Sons, Inc.
Model calculations for small closed‐ring CdS clusters and chemisorption processes by a quantum chemical cluster approach
Authors: Tóth Katalin , Pakkanen Tapani A.
Published: January 2005

Chemisorption on small, closed‐ring CdS clusters and the electronic structure of the surface were studied using Hartree–Fock valence calculations based upon stepwise density matrix approximations. Detailed valence calculations gave stabilization energies similar to the all‐electron results for the small CdS clusters, verifying our valence method in which the approximations of the density matrices were fitted against the atomic calculations. Chemisorption studies have shown that the 4d shell relaxation on the Cd atom plays a crucial role even though the 4d does not participate directly in the substrate–adsorbate bonds. Thus, the CdCl2 was found unbound to the surface in the case of implicit description of the 4d orbital of the Cd whereas treating the Cd 4d orbital explicitly in the variational calculation the CdCl2 bonds to the surface with the calculated adsorption energy of 107.4 kJ/mol. © 1993 John Wiley & Sons, Inc.
Path integral theory: An improved simulation for the forces in semiclassic systems
Authors: Morales Juan J.
Published: January 2005

A method is proposed for calculating the forces in path integral theory and tested on semiclassic systems. It takes the range of the classic and quantum interactions into account and uses a second table within the neighbors table for the nearest neighbors. This method is found to be much more efficient than either the standard direct method or the traditional neighbors table, the efficiency increasing with the size of the system. The method can also be applied to clusters whose interaction centers are much farther apart than the distances between two consecutive members of the cluster. © 1993 John Wiley & Sons, Inc.
A critical comparison of search algorithms applied to the optimization of protein side‐chain conformations
Authors: Tufféry P. , Etchebest C. , Hazout S. , Lavery R.
Published: January 2005

Three different optimization algorithms are applied to solving the problem of finding the best side‐chain conformations with a test set of 14 globular proteins having known crystallographic conformations. It is shown that simulated annealing, simple and modified genetic algorithms, and a heuristic combinatorial approach achieve similar optimal solutions, with the exception of simulated annealing applied to the largest proteins. The efficiency of the different algorithms, however, shows wide variations. General conclusions are drawn concerning the optimal approach to such problems. © 1993 John Wiley & Sons, Inc.
Conformational dependence of electrostatic potential‐derived charges: Studies of the fitting procedure
Authors: Stouch Terry R. , Williams Donald E.
Published: January 2005

Atomic monopole “point charges” are routinely determined through a least squares fit to molecular electrostatic potentials [potential‐derived (PD) charges]. Previously, it has been shown that these charges vary with variation in molecular conformation. Also, it has been observed that these swings in charges are highly correlated between neighboring atoms. Here, we examine the least squares variance–covariance data matrices for a set of data in the literature and find further indications of high colinearity within the data. These colinearities effectively reduce the dimensionality of the data to a value well below the number of atoms in the molecules. This suggests that the data is not of sufficient dimensionality to support calculation of the charges for all of the atoms in a statistically significant way. We experiment with fixing the charges of atoms whose PD charges reflect large errors in the fit. The resulting estimates of fit of the remaining charges are little degraded from the estimates of fit when the charges of all of the atoms are fit. In addition, the charges that are fit take what would be considered more reasonable and “chemically intuitive” values, often of smaller magnitude. Although most of the free charges continue to vary with molecular conformation, their range is no larger than when all charges were fit and, in some cases, the ranges of the charges for the fit atoms is actually reduced over those that are found when all of the atoms take part in the fitting procedure. The errors of fit are lower and the unconstrained charges appear more reasonable when more chemically “reasonable” charges are used for the fixed values. This suggests that in many cases charges are transferable between molecules. Further, it shows a way to justifiably reduce the large fluctuations in PD charges that occur with variations in conformation. © 1993 John Wiley & Sons, Inc.
Molecular dynamics of 18‐crown‐6 complexes with alkali–metal cations and urea: Prediction of their conformations and comparison with data from the cambridge structural database
Authors: Leuwerink E.T.H. , Harkema S. , Briels W.J. , Feil D.
Published: January 2005

Complexes of 18‐crown‐6 with alkali–metal cations (Na+, K+, and Rb+), urea, and the uncomplexed crown ether were studied in vacuo with the molecular dynamics method. Conformational data from these calculations (simulation times in the range from 6–15 ns) was compared with information from the Cambridge Structural Database. Despite the differences in condition between the simulations and the solid state, a number of interesting similarities are observed. © 1993 John Wiley & Sons, Inc.
AQUARIUS2: Knowledge‐based modeling of solvent sites around proteins
Authors: Pitt William R. , Murray‐Rust Judith , Goodfellow Julia M.
Published: January 2005

The program AQUARIUS2 calculates probable positions for water molecules within the first hydration shell of any protein for which atomic coordinates are known. Like its predecessor, AQUARIUS, it uses a knowledge of water molecules sites from crystallographically determined protein structures. Energy calculations are not employed. It differs substantially from the original program in that a 3‐D probability map (for solvent sites) is generated around the surface of the protein instead of the previously used discrete points. The accuracy of the program has been gauged by comparison with experimentally derived water molecule positions for proteins not used in the knowledge base of the program. It has also been tested by combining the probability density maps with crystallographically determined electron density maps for the protein porphobilinogen deaminase. This procedure filters the most likely solvent electron density peaks from the background noise and has been used in the determination of the solvent structure around the protein nerve growth factor. © John Wiley & Sons, Inc.
Quantification of substituent and ligand size by the use of solid angles
Authors: White David , Taverner B. Craig , Leach P.G.L. , Coville Neil J.
Published: January 2005

A new, generalized, method for measuring the steric size of ligands and substituents has been developed. The method is based on the solid angle concept, the solid angle being generated by the pairwise addition of spheres (atoms). The problem of overlapping spheres (atoms) has been solved analytically and the algorithm provided permits evaluation of the steric space occupied by any combination of spheres (atoms). A range of solid angles for commonly encountered ligands and substituents has been determined and compared to literature values for linear cone angles. © John Wiley & Sons, Inc.
LIN: A new algorithm to simulate the dynamics of biomolecules by combining implicit‐integration and normal mode techniques
Authors: Zhang Guihua , Schlick Tamar
Published: January 2005

A central goal in molecular dynamics simulations is increasing the integration time‐step to allow the capturing of biomolecular motion on biochemically interesting time frames. We previously made a step in that direction by developing the Langevin/implicit–Euler scheme. Here, we present a modified Langevin/implicit–Euler formulation for molecular dynamics. The new method still maintains the major advantage of the original scheme, namely, stability over a wide range of time‐steps. However, it substantially reduces the damping effect of the high‐frequency modes inherent in the original implicit scheme. The new formulation involves separation of the solution into two components, one of which is solved exactly using normal‐mode techniques, the other of which is solved by implicit numerical integration. In this way, the high‐frequency and fast‐varying components are well resolved in the analytic solution component, while the remaining components of the motion are obtained by a large time‐step integration phase. Full details of the new scheme are presented, accompanied by illustrative examples for a simple pendulum system. An application to liquid butane demonstrates stability of the simulations at time‐steps up to 50 fs, still with activation of the high‐frequency modes. © John Wiley & Sons, Inc.
Optimization and application of lithium parameters for PM3
Authors: Anders Ernst , Koch Rainer , Freunscht Peter
Published: January 2005

Lithium parameters have been optimized for Stewart's standard PM3 method. The average deviation of the heats of formation calculated for 18 reference compounds is 6.2 kcal/mol from the experimental or high‐level ab initio data; the average deviation with Li/MNDO is 18.9 kcal/mol. The average error in bond lengths is also reduced by a factor of two to three. Ionization potentials and dipole moments are reproduced with comparable accuracy than Li/MNDO. However, the mean deviation for the heats of formation of both methods increases when being applied to other systems, especially to small inorgnic molecules. The applicability of the new parameter set is demonstrated further for various compounds not included in the reference set, for the calculation of the activation barriers of several lithiation reactions, as well as for the estimation of oligomerization energies of methyl lithium (including the tetramer). Li/PM3 gives reliable results even for large dimeric complexes, like [{4‐(CH3CR)C5H4N}Li]2, containing TMEDA or THF as coligands and reproduces the haptotropic interaction between Li+ and π‐systems (e.g., in benzyl lithium) as well as the relative energies and structural features of compounds with “hypervalent” atoms (e.g., in lithiated sulfones). © John Wiley & Sons, Inc.
Comparison of atomic charges derived via different procedures
Authors: Wiberg Kenneth B. , Rablen Paul R.
Published: January 2005

Atomic charges were obtained fromab initiomolecular orbital calculations using a variety of procedures to compare them and assess their utility. Two procedures based on the molecular orbitals were examined, the Mulliken population analysis and the Weinhold–Reed Natural Population Analysis. Two procedures using the charge density distribution were included; the Hirshfeld procedure and Bader's Atoms in Molecules method. Charges also were derived by fitting the electrostatic potential (CHELPG) and making use of the atomic polar tensors (GAPT). The procedures were first examined for basis set independence, and then applied to a group of hydrocarbons. The dipole moments for these molecules were computed from the various atomic charges and compared to the total SCF dipole moments. This was followed by an examination of a series of substituted methanes, simple hydrides, and a group of typical organic compounds such as carbonyl derivatives, nitriles, and nitro compounds. In some cases, the ability of the charges to reproduce electrostatic potentials was examined. © John Wiley & Sons, Inc.
Comparison of NDDO and quasi‐ab initio approaches to compute semiempirical molecular electrostatic potentials
Authors: Alhambra C. , Luque F. J. , Orozco Modesto
Published: January 2005

The suitability of the two most widely used strategies to compute semiempirical MEPs is examined. For this purpose, MEP minima, electrostatic charges, and dipoles for a large number of molecules were computed at the AM1, MNDO, and PM3 levels using both the NDDO strategy developed by Ferenczy, Reynolds, and Richards and our own quasi‐ab initio method. Results demonstrate that the quasi‐ab initio is preferred over the NDDO method for the computation of MEP minima. It is also found that the best set of semiempirical charges and dipoles are obtained using either the AM1 NDDO or the MNDO quasi‐ab initio methods. In these two cases, the quality of the results is fully comparable with 6‐31G* values. © 1994 by John Wiley & Sons, Inc.
Display of the flow of energy in molecules
Authors: Schwieters Charles D. , Rabitz Herschel
Published: January 2005

In this article, we develop a method to graphically display the flow of energy within molecules. An energy continuity equation is derived leading to a molecular energy flux vector field. Computation of the flux calls for the intramolecular potential, any external interactions, and the phase space trajectories of the molecular motion. The flux provides a means to display energy flow in still frames and as a tool to visualize hitherto undiscovered dynamic pathways in molecules. Examples are presented that show energy flow in three molecular systems and illustrate the point that depiction of energy flux patterns has increasing utility and meaning as one moves to larger molecules. Simple extensions to this work would also allow visualization of the flux of such quantities as linear and angular momentum. © 1994 by John Wiley & Sons, Inc.
Conformation and reactivity of α‐oxo‐ketenes: Ab initio and semiempirical (AM1, PM3) calculations
Authors: Janoschek Rudolf , Fabian Walter M. F. , Kollenz Gert , Oliver Kappe C.
Published: January 2005

Ab initio MP2/6‐31G*//MP2/6‐31G* and semiempirical AM1 and PM3 calculations on a series of differently substituted α‐oxo‐ketenes are used to investigate E/Z‐isomerism and rotational barriers in these molecules. Sterically crowded derivatives are found to exist solely as s‐E conformers. The unusual stability of these derivatives thus can be attributed to their inability to adopt the s‐Z conformation required for the normal α‐oxo‐ketene reactions. With respect to structures and energies, the PM3 method (especially in the case of highly crowded molecules) is found to be less reliable than AM1. Ab initio HF/3‐21G and PM3 vibrational frequencies appear to be of sufficient accuracy for a distinction between s‐Z and s‐E conformers. In this respect, the AM1 method appears less reliable. © 1994 by John Wiley & Sons, Inc.
Parallel algorithm for calculating ro‐vibrational states of diatomic molecules
Authors: Neto J. J. Soares
Published: January 2005

In this article, we develop and implement an algorithm for calculating the rovbrational states of diatomic molecules optimized for multiple instructions multiple data computers of distributed memory. The method is based upon the p‐version of the finite element method and has been implemented on an INTEL iPSC/2 machine with 16 processors. © 1994 by John Wiley & Sons, Inc.
Free energy of solvation of a small Lennard–Jones particle
Authors: Lin Ching‐Lung , Wood Robert H.
Published: January 2005

In molecular dynamics (MD) and Monte Carlo (MC) free energy calculations, the choices of the thermodynamic paths from state a to state b affect the accuracy of the result and the efficiency of the programs. Most of the problems occur at the initial stages of growing in a new particle into a solvent. Based on statistical mechanical perturbation theory, an accurate and efficient direct calculation of inserting a small Lennard–Jones particle into solvent is derived. This eliminates the need for calculation of the initial stages of growing in a new particle by MD or MC simulation. Examples are given to show the utility of direct calculation. The recommended procedure is to use direct calculation for a small Lennard–Jones particle and then use MD or MC simulations to calculate the ΔG of changing the small Lennard–Jones particle into the target molecule. © 1994 by John Wiley & Sons, Inc.
Atomic charges derived from a fast and accurate method for electrostatic potentials based on modified AM1 calculations
Authors: Wang Bingze , Ford George P.
Published: January 2005

Atomic charges derived from a recently described approach to the very rapid computation of AM1 electrostatic potentials (ESP) accurately parallel, but are ca. 20% smaller than, the corresponding HF/6‐31G* values. The dipole moments computed from the AM1 charges are virtually identical to those derived directly from the wave function and in rather better agreement with the experimental values than those computed using the HF/6‐31G* charges. Unlike other approaches to the semiempirical calculation of ESP‐derived charges, the present method also yields near HF/6‐31G* quality potentials close to the molecular periphery. For medium‐sized organic molecules (40‐100 basis functions), the method is approximately two orders of magnitude faster than those involving prior deorthogonalization of AM1 wave function and explicit computation of the full ESP integral matrix. © 1994 by John Wiley & Sons, Inc.
The structures of LiNC, NaNC, and KNC: Potential energy surface for the orbiting motion of the metal cation around the CN group
Authors: Dorigo Andrea , von Ragué Schleyer Paul , Hobza Pavel
Published: January 2005

Sets of XNC (X = Li, Na, and K) structures have been investigated using a variety of theoretical methods and basis sets. Two linear and a bridged structure correspond to an energy minimum for LiCN. For NaCN and KCN, the linear isocyanide is a minimum at most levels of theory but becomes a second‐order stationary point when correlated levels and large basis sets are used. Two transition structures are involved in the interconversion of the bridged form and each linear isomer. The isomerization of the bridged minimum to the linear XCN involves a substantial barrier in each case, so that the satellite motion of the metal is facile at one end but not at the other. Calculations with large basis sets and with electron correlation, fourth‐order Møller–Plesset theory for KNC, and quadratic configuration interaction [QCISD(T)] for LiNC and NaNC give qualitative and quantitative agreement with this experiment. The sodium and potassium cyanide prefer bridged forms, in contrast to the linear isocyanide LiNC. © 1994 by John Wiley & Sons, Inc.
Relativistic Dirac–Fock calculations for closed‐shell molecules
Authors: Pisani L. , Clementi E.
Published: January 2005

A new code has been written to perform relativistic Dirac–Fock self‐consistent field (SCF) calculations on closed‐shell molecules of any symmetry. The choice of the basis set allows us to work at different levels of approximation depending on the precision required. Calculations on the H2Po molecule show that accurate results on specific problems like geometry optimization can be obtained by evaluating the two‐electron integrals on half the basis spinors. © 1994 by John Wiley & Sons, Inc.
Effect of charge on bond strength in hydrogenated amorphous silicon
Authors: Clare B. W. , Talukder G. , Jennings P. J. , Cornish J. C. L. , Hefter G. T.
Published: January 2005

We have studied the effect of excess charge on the bond strength in the silanes SiH4 and Si2H6 to assess whether charge trapping in a solid‐state lattice might promote the technologically important photodegradation of amorphous silicon alloys (the Staebler‐Wronski effect). The calculations indicate that both positive and negative charges reduce the strength of SiH and SiSi bonds considerably, to the point where they may be broken easily by visible or even infrared light. © 1994 by John Wiley & Sons, Inc.
Hash codes for the identification and classification of molecular structure elements
Authors: Ihlenfeldt Wolf Dietrich , Gasteiger Johann
Published: January 2005

A set of algorithms is presented which establish the topological identity of atoms, bonds, molecules, and ensembles of molecules from a basic connection table. The computationally inexpensive result is a fixed‐length hash code which is suited for database applications and structure manipulation programs. The degree of differentiation between structural entities is adjusted easily for stereocenters, isotope labeling, atomic charges, and ionization locations or other properties. Special algorithms are presented which deal with problematic cases of uniform atomic environments. A number of practical applications demonstrate the usefulness of these hash codes. © 1994 by John Wiley & Sons, Inc.
New implementation of a program to calculate correlated band structures of polymers: An application to the band structure of polyparaphenylene (PPP)
Authors: Palmer Ian J. , Ladik Janos
Published: January 2005

A new program has recently been implemented with the aim of extending quasi‐particle (QP) band structure calculations to polymers with larger unit cells. The theoretical background is briefly reviewed and the new algorithm described, which has been optimized for machines with vector processors. To illustrate the usefulness of this technique, calculations have been performed on polyparaphenylene (PPP) using a double‐zeta basis set. The calculated QP band gap between the valence and conduction bands is 2.3 eV, which compares favorably with the experimental value of 2.8 eV. The self‐consistent field (SCF) result with the same double‐zeta basis set is 8.7 eV. © 1994 by John Wiley & Sons, Inc.
Cluster analysis of molecular conformations
Authors: Shenkin Peter S. , McDonald D. Quentin
Published: January 2005

We describe a method for locating clusters of geometrically similar conformers in ensembles of chemical conformations. We first calculate the pairwise interconformational distance matrix in either torsional or Cartesian space and then use an agglomerative, single‐link clustering method to define a hierarchy of clusterings in the same space. Especially good clusterings are distinguished by high values of the separation ratio: the ratio of the shortest intercluster distance to the characteristic threshold distance defining the clustering. We also discuss other statistics. The method has been embodied in a program called XCluster, which can display the distance matrix, the hierarchy of clusterings, and the clustering statistics in a variety of formats. XCluster can also write out the clustered conformations for subsequent or simultaneous viewing with a molecular visualization program. We demonstrate the sorts of insight that this approach affords with examples obtained from conformational search and molecular dynamics procedures. © 1994 by John Wiley & Sons, Inc.
On the functional representation of bond energy functions
Authors: Dinur U. , Hagler A. T.
Published: January 2005

Ab initio calculations are used to test the ability of various representations to reproduce bond energies. It is found that expansion in 1/R, where R is the bond length, is remarkably efficient and is consistently better than the usual R expansion. A quadratic form in 1/R is better than a cubic representation in R and sometimes even as good as a quartic representation. A cubic function in 1/R is, in all cases studied, better performing than the quartic expansion in R. It is also found that parameters derived with the 1/R expansion are defined more sharply than those derived for the R expansion. It is suggested that the 1/R expansion may be computationally more efficient for simulations of large biomolecules and for constructions of reactive force fields than the standard bond functions. © 1994 by John Wiley & Sons, Inc.
The valence isomers of (CH)8 and (SiH)8: An ab initio MO study
Authors: Versteeg Uwe , Koch Wolfram
Published: January 2005

The 22 possible valence isomers of the (CH)8 and (SiH)8 systems have been studied by ab initio molecular orbital calculations at the MP2/6‐31G*//6‐31G* + ZPE level. Optimized geometries, relative energies, and, for some selected compounds, vibrational frequencies are reported. The systematic differences between the carbon and silicon compounds are analyzed. © 1994 by John Wiley & Sons, Inc.
Gaussian multipoles in practice: Electrostatic energies for intermolecular potentials
Authors: Wheatley Richard J. , Mitchell John B. O.
Published: January 2005

A method is presented for calculating the total electrostatic interaction energies between molecules from ab initio monomer wave functions. This approach differs from existing methods, such as Stone's distributed multipole analysis (DMA), in including the short‐range penetration energy as well as the long‐range multipolar energy. The monomer charge densities are expressed as distributed series of atom‐centered functions which we call Gaussian multipoles; these are analogous to the distributed point multipoles used in DMA. Our procedure has been encoded in the GMUL program. Calculations have been performed on the formamide/formaldehyde complex, a model system for NH …︁ O hydrogen bonding in biological molecules, and also on guanidinium/benzene, modeling amino/aromatic interactions in proteins. We find that the penetration energy can be significant, especially in its contribution to the variation of the electrostatic energy with interaction geometry. A hybrid method, which uses Gaussian multipoles for short‐range atom pair interactions and point multipoles for long‐range ones, allows the electrostatic energies, including penetration, to be calculated at a much reduced cost. We also note that the penetration energy may provide the best route to an atom–atom anisotropic model for the exchange‐repulsion energy in intermolecular potentials. © 1994 by John Wiley & Sons, Inc.
Reversed stereochemical preference in binding of Ro 31‐8959 to HIV‐1 proteinase: A free energy perturbation analysis
Authors: Rao B. G. , Murcko M. A.
Published: January 2005

Ro 31‐8959 is a highly potent inhibitor of HIV‐1 proteinase in phase III clinical trials for treatment of AIDS. It is also the first subnanomolar inhibitor that demonstrated reversed stereochemical preference at the central hydroxyl group. Free energy perturbation calculations have been carried out to rationalize the preference for the R‐diastereomer by consideration of two models of the (weaker) S‐diastereomer. In the first model, the central hydroxyl group makes only one hydrogen bond with the active site aspartates, whereas the hydroxyl group in the second model makes at least three strong hydrogen bonds. Using the first model, the free energy difference in binding of Ro 31‐8959 and its S‐diastereomer is calculated to be 3.4 kcal/mol, which is in close agreement with the experimental value. Although the second model has a more favorable interaction with the active site aspartates compared to the first model, it has a higher energy N‐axial conformation at the decahydroisoquinoline group in P. We show here that the two contributions cancel each other and the two models of S‐diastereomer are predicted to have equivalent binding. The stereochemical preference in a hydroxyethylamine series of inhibitors appears to be affected by both intermolecular and intramolecular (conformational) energies. The binding data on the proline containing inhibitors are rationalized based on these results. © 1994 by John Wiley & Sons, Inc.
Stability of two‐dimensional crystalline aggregates of a protein studied by molecular dynamics
Authors: Higo Junichi , Yamaki Mariko , Hogyoku Michiru , Takahashi Takuya , Endo Shigeru , Nagayama Kuniaki
Published: January 2005

Two‐dimensional protein (ferritin) aggregates with a square lattice symmetry, which were formed within a thin liquid layer on a mercury surface, were studied by molecular dynamics (MD) simulation. For the simulation, the ferritin molecule was modeled by an assembly of 49 spheres, and the intermolecular interactions were given by simple formulae. During the simulation, molecules were confined within a layer, which corresponds to the thin liquid layer. An annealing MD simulation was done starting from a random molecular configuration within the layer, and aggregates with the square lattice symmetry were also obtained. To study the stability of aggregates, dissociation processes of the aggregates were analyzed using MD simulations at room temperature. Interactions between the nearest‐neighbor molecules were regarded as bonds. Mean bond energies and correlation coefficients between the bond energies were calculated from the MD trajectories. A decay profile according to the dissociation was obtained, yielding a dissociation rate constant. Buried bonds were stronger than peripheral bonds. The larger the aggregate size, the stronger the bond for each of the buried and peripheral bonds. A simple theoretical account, which is applicable to a general bonded network, was introduced to analyze the dynamics of the aggregates. © 1994 by John Wiley & Sons, Inc.
Application of a high‐performance, special‐purpose computer, GRAPE‐2A, to molecular dynamics
Authors: Higo Junichi , Endo Shigeru , Nagayama Kuniaki , Ito Tomoyoshi , Fukushige Toshiyuki , Ebisuzaki Toshikazu , Sugimoto Daiichiro , Miyagawa Hiroo , Kitamura Kunihiro , Makino Junichiro
Published: January 2005

The special‐purpose computer GRAPE‐2A accelerates the calculation of pairwise interactions in many‐body systems. This computer is a back‐end processor connected to a host computer through a Versa Module Europe (VME) bus. GRAPE‐2A receives coordinates and other physical data for particles from the host and then calculates the pairwise interactions. The host then integrates an equation of motion by using these interactions. We did molecular dynamics simulations for two systems of liquid water: System 1 (1000 molecules), and System 2 (1728 molecules). The time spent for one step of molecular dynamics was 3.9 s (System l), and 10.2 s (System 2). The larger the molecular system, the higher the performance. The speed of GRAPE‐2A did not depend on the formula describing the pairwise interaction. The cost performance was about 20 times better than that of the fastest workstations available today, and GRAPE‐2A cost only $22,000. © 1994 by John Wiley & Sons, Inc.
An algorithm for packing regular multistrand polypeptide structures by energy minimization
Authors: Gibson Kenneth D. , Scheraga Harold A.
Published: January 2005

An algorithm has been developed for packing polypeptide chains by energy minimization subject to regularity conditions, in which regularity is maintained without the addition of pseudoenergy terms by defining the energy as a function of appropriately chosen independent variables. The gradient of the energy with respect to the independent variables is calculated analytically. The speed and efficiency of convergence of the algorithm to a local energy minimum are comparable to those of existing algorithms for minimizing the energy of a single polypeptide chain. The algorithm has been used to reinvestigate the minimum‐energy regular structures of three‐stranded (L‐Ala)8, three‐stranded (L‐Val)6, five‐stranded (L‐Ile)6, and the regular and truncated three‐stranded (Gly‐L‐Pro‐L‐Pro)4 triple helices. Local minima with improved packing energies, but with essentially unchanged geometrical properties, were obtained in all cases. The algorithm was also used to reinvestigate the structures proposed previously for the I and II forms of crystalline silk fibroin. The silk II structure was reproduced with slightly improved packing and little other change. The orthorhombic silk I structure showed more change and considerably improved packing energy, but the new regular monoclinic silk I structure had considerably higher energy. The results support the structure proposed previously for silk II and the orthorhombic structure, but not the monoclinic structure proposed for silk I. © 1994 by John Wiley & Sons, Inc.
An application of the Miertus‐Scrocco‐Tomasi solvation model in molecular mechanics and dynamics simulations
Authors: Varnek A. A. , Wipff G. , Glebov A. S. , Feil D.
Published: January 2005

The point‐chart approximation of the Miertus‐Scrocco‐Tomasi solvation model (MST‐PC) based on a continuum representation of the solvent has been incorporated in force field calculations. Application in molecular mechanics (MM) involves conformational equilibria in solution: rotational isomers of ethylene glycol (I), 1,2‐difluoreothane (II), fluoroacetic acid (III), and representative conformers of macrocyclic receptors such as 18‐crown‐6 (IV), cryptand 2.2.2 (V), and t‐butyl‐calix[4]arenetetraamide (VI). Assessment of the MST‐PC results is based on the comparison with ab initio reactive field calculations (for I–III), with the continuum model of Still (W. C. Still et al., J. Am. Chem. Soc., 1990, 112, 6127) (for I–VI), and with average solute–solvent interaction energies obtained from molecular dynamics (MD) simulations with explicit solvent in water (I–VI) and in acetonitrile (IV–VI). It is demonstrated that the continuum solvent model qualitatively reproduces the trends in solvation energies in water. The few exceptions may be related to particular topological features of the solute. An improved discrete/continuum approach in which some first‐shell solvent molecules are considered as a part of the solute embedded in the dielectric continuum provides more realistic results, as is shown for VI in water. The MST‐PC model which mimics the solute–solvent electrostatic interaction only fails to reproduce conformationally dependent solvation energies in acetonitrile, in which the electrostatic contribution is relatively small compared to van der Waals interactions. Exploratory MD simulations within the continuum model in water are reported on urea and 18‐crown‐6. © 1995 by John Wiley & Sons, Inc.
Monte Carlo study of lipid membranes: Simulation of diparmitoylphosphatidylcholine bilayers in gel and liquid‐crystalline phases
Authors: Taga Tooru , Masuda Kazuhumi
Published: January 2005

The statistical properties of the bilayer membranes of diparmitoylphosphatidylcholine (DPPC) in the gel and liquid‐crystal phases were studied by Monte Carlo (MC) simulation using potential functions of the Lennard‐Jones, the simple Coulomb, and the bond torsion. The simulation was undertaken on a two‐dimensional periodic condition imposed on the bilayer model consisting of faithfully described molecules. The structure and ordering of the model bilayers accorded well with experiments, and the segment order parameters were in agreement with those of the nuclear magnetic resonance (NMR) experiments. The two kinds of lipid chains of DPPC do not equivalently behave in the bilayers, and chain 2 has lower ordering than chain 1. The order parameters of the first eight segments of chain 2 in the liquid‐crystal model are particularly small and are roughly constant. From electron density analysis, it has been observed that the liquid‐crystal bilayer has about one excess water molecule per one lipid molecule in comparison with the gel bilayer. The energy difference between the two bilayer models, taking account of the water contribution, is consistent with the latent heat of the phase transition. © 1995 by John Wiley & Sons, Inc.
A molecular mechanical model that reproduces the relative energies for chair and twist‐boat conformations of 1,3‐dioxanes
Authors: Howard Allison E. , Cieplak Piotr , Kollman Peter A.
Published: January 2005

We present molecular mechanics calculations on the conformational energies of several 2,2‐dimethyl‐trans‐4,6‐disubstituted‐1,3‐dioxanes. Previous studies by Rychnovsky et al.1 have suggested that the relative conformational energies of chair and twist‐boat forms of these 1,3‐dioxanes were poorly represented by the molecular mechanical models MM2* and MM3* (MacroModel2 implementations of MM2 and MM3) both when compared to experiment and to high‐level quantum mechanical calculations. We have studied these molecules with a molecular mechanical force field which features electrostatic‐potential‐based atomic charges. This model does an excellent job of reproducing the relative conformational energies of the highest level of theory (MP2/6‐31G*) applied to the problem. Furthermore, when empirically corrected using the MP2/6‐31G* relative conformational energies of the unsubstituted compound 2,2,4‐trimethyl‐1,3‐dioxane, the absolute energy differences calculated with this new model between the chair and twist‐boat conformers for five substituted compounds are within an average of 0.30 kcal/mol of the MP2/6‐31G* values. The correlation with experiment is also very good. One can, however, modify the initial molecular mechanical model with a single V1(OCOC) torsional potential and do an excellent job in reproducing the absolute conformational energies of the dioxanes as well, with an average error in conformational energies of 0.45 kcal/mol. This same torsional potential was independently developed by comparing ab initio and molecular mechanical energies of the molecule 1,1‐dimethoxymethane. Thus, we have succeeded in developing a general molecular mechanical model for 1,3‐dioxoalkanes. In addition, we have compared the standard MM2 and MM3 models with MM2* and MM3* (ref. 2) and have found some significant differences in relative conformational energies between MM2 and MM2*. MM2 has an improved correlation with the best ab initio data compared to MM2* but is still significantly worse than that found with lower‐level ab initio or AM1 semiempirical quantum mechanics or the new molecular mechanical model presented here. MM3 leads to conformational energies very similar to MM3*. Energy component analysis suggests that the single most important element in reproducing the conformational equilibrium is the electrostatic energy. This fact rationalizes the success of AMBER models, whose fundamental tenet is the accurate representation of quantum mechanically calculated molecular electrostatic effects. © 1995 by John Wiley & Sons, Inc.
An application of the reaction field theory to hydrated metal cations in the framework of the MNDO, AM1, and PM3 methods
Authors: Furuki Takao , Sakurai Minoru , Inoue Yoshio
Published: January 2005

A reaction field theory, combined with the MNDO, AM1, and PM3 molecular orbital methods, was applied to hydration phenomena of metal cationic species. The first hydration shell was treated explicitly by using a supermolecular model, [M(H2O)n]m+, and its surrounding medium was described with a continuum dielectric. Hydration free energies were evaluated as a sum of the contributions from the electrostatic interaction with the bulk medium, the hydrated cluster formation, the cavity formation, and the vaporization of water molecules forming the cluster. As a whole, calculated hydration energies were in good agreement with the corresponding experimental data over various kinds of metal cationic species. © 1995 by John Wiley & Sons, Inc.
Intervals and the deduction of drug binding site models
Authors: Crippen Gordon M.
Published: January 2005

In the search for new drugs, it often occurs that the binding affinities of several compounds to a common receptor macromolecule are known experimentally, but the structure of the receptor is not known. This article describes an extraordinarily objective computer algorithm for deducing the important geometric and energetic features of the common binding site, starting only from the chemical structures of the ligands and their observed binding. The user does not have to propose a pharmacophore, guess the bioactive conformations of the ligands, or suggest ways to superimpose the active compounds. The method takes into account conformational flexibility of the ligands, stereospecific binding, diverse or unrelated chemical structures, inaccurate or qualitative binding data, and the possibility that chemically similar ligands may or may not bind to the receptor in similar orientations. The resulting model can be viewed graphically and interpreted in terms of one or more binding regions of the receptor, each preferring to be occupied by various sorts of chemical groups. The model always fits the given data completely and can predict the binding of any other ligand, regardless of chemical structure. The method is an outgrowth of distance geometry and Voronoi polyhedra site modeling but incorporates several novel features. The geometry of the ligand molecules and the site is described in terms of intervals of internal distances. Determining the site model consists of reducing the uncertainty in the interregion distance intervals, and this uncertainty is described as intervals of intervals. Similarly, the given binding affinities and their experimental uncertainties are treated as intervals in the affinity scale. The final site model specifies an entire region of interaction energy parameters that satisfy the training set rather than a single set of parameters. Predicted binding for test compounds results in an interval which, when compared to the experimental interval, may be correct, incorrect, or vague. There is a pervasive ternary logic involved in the assessment of predictions, in the search for a satisfactory model, and in judging whether a given molecule may bind in a particular orientation: true, false, or maybe. The approach is illustrated on an extremely simple artificial example and on a real data set of cocaine analogues binding to a nerve membrane receptor in vitro. © 1995 by John Wiley & Sons, Inc.
Calculating the electric potential of macromolecules: A simple method for molecular surface triangulation
Authors: Zhexin Xiang , Yunyu Shi , Yingwu Xu
Published: January 2005

An improved version of the “marching‐cube” method1 is proposed for molecular surface triangulation. This new algorithm involves fewer and simpler basic building blocks and avoids the artificial gaps of the original one. Moreover, to make it applicable to the boundary element method, the procedures for the protein cavity identification and triangle reduction are also presented. The triangulation procedure was tested by incorporating it into the boundary element method (BEM) to estimate the pKa values of subtilisin BPN′ and bovine trypsin inhibitor (BPTI). © 1995 by John Wiley & Sons, Inc.
Analytical approach to very large benzenoid polymers
Authors: Živković T. , Randić M. , Klein D. J. , Zhu H.‐Y. , Trinajstić N.
Published: January 2005

We consider rigorous evaluation of conjugated‐circuit resonance energies for families of structurally related benzenoid hydrocarbons of increasing size. Local and global aromatic properties of such molecules are investigated with particular interest in modeling high polymers. Using the algebra of large numbers, exact formulas for contributions from individual benzene rings of polymers with up to 25,000 repeating units (close to half a million carbon atoms) were derived. All arithmetic procedures were carried out in terms of whole numbers retaining all digits, of which there were sometimes more than 105. © 1995 by John Wiley & Sons, Inc.