bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intervals and the deduction of drug binding site models
Authors: Crippen Gordon M. 
Published: January 2005

AbstractIn 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

AbstractAn 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

AbstractWe 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.
On the accuracy of density functionals and their basis set dependence: An extensive study on the main group homonuclear diatomic molecules Li2 to Br2
Authors: Hertwig Roland H. , Koch Wolfram 
Published: January 2005

AbstractThe equilibrium bond distances, harmonic frequencies, and bond dissociation energies of the 21 homonuclear diatomics Li2—F2, Na2—Cl2, and K2—Br2 have been determined using approximate density functional theory (DFT) employing various widely used functionals and basis sets ranging from single zeta to triple zeta plus polarization quality. The results are in general much less sensitive to the size of the basis set as in conventional ab initio molecular orbital (MO) theory, while the choice of the functional is of much more significance. For one basis set (6‐311G*), the performance of the DFT‐based calculations has been compared and found to be superior to Hartree‐Fock (HF) Møller Plesset second order perturbation theory (MP2), or configuration interaction with single and double excitations (CISD) calculations. Particularly, no pathological cases, such as the group 2 dimers (Be2, Mg2, Ca2), are observed. © 1995 by John Wiley & Sons, Inc.
Unusual conformational‐determining interactions in oxymethylpyridines: An ab initio study and an improved method for refining molecular mechanics parameters
Authors: Norrby Per‐Ola , Wärnmark Kenneth , Åkermark Björn , Moberg Christina 
Published: January 2005

AbstractThe conformational preferences of oxymethylpyridines have been investigated by ab initio calculations and compared to similar calculations for oxymethylbenzene. The CO bond in the pyridine compounds was found to prefer eclipsing with a CC bond in the ring, in agreement with previous observations but in disaccord with tentative MM2 calculations. The effect was most pronounced in the 2‐substituted pyridine. The benzene compound, on the other hand, showed good agreement between the energies from MM2, MM3, and ab initio calculations. The conformational preferences are discussed in terms of stereoelectronic interactions. New MM2 and MM3 parameters were determined from ab initio calculations on nonstationary points on the energy hypersurface. The parameterization method is discussed. © 1995 by John Wiley & Sons, Inc.
Accurate modeling of the intramolecular electrostatic energy of proteins
Authors: Dudek Michael J. , Ponder Jay W. 
Published: January 2005

AbstractThe (ϕ, ψ) energy surface of blocked alanine (N‐acetyl–N′‐methyl alanineamide) was calculated at the Hartree‐Fock (HF)/6‐31G* level using ab initio molecular orbital theory. A collection of six electrostatic models was constructed, and the term electrostatic model was used to refer to (1) a set of atomic charge densities, each unable to deform with conformation; and (2) a rule for estimating the electrostatic interaction energy between a pair of atomic charge densities. In addition to two partial charge and three multipole electrostatic models, this collection includes one extremely detailed model, which we refer to as nonspherical CPK. For each of these six electrostatic models, parameters—in the form of partial charges, atomic multipoles, or generalized atomic densities—were calculated from the HF/6‐31G* wave functions whose energies define the ab initio energy surface. This calculation of parameters was complicated by a problem that was found to originate from the locking in of a set of atomic charge densities, each of which contains a small polarization‐induced deformation from its idealized unpolarized state. It was observed that the collective contribution of these small polarization‐induced deformations to electrostatic energy differences between conformations can become large relative to ab initio energy differences between conformations. For each of the six electrostatic models, this contribution was reduced by an averaging of atomic charge densities (or electrostatic energy surfaces) over a large collection of conformations. The ab initio energy surface was used as a target with respect to which relative accuracies were determined for the six electrostatic models. A collection of 42 more complete molecular mechanics models was created by combining each of our six electrostatic models with a collection of seven models of repulsion + dispersion + intrinsic torsional energy, chosen to provide a representative sample of functional forms and parameter sets. A measure of distance was defined between model and ab initio energy surfaces; and distances were calculated for each of our 42 molecular mechanics models. For most of our 12 standard molecular mechanics models, the average error between model and ab initio energy surfaces is greater than 1.5 kcal/mol. This error is decreased by (1) careful treatment of the nonspherical nature of atomic charge densities, and (2) accurate representation of electrostatic interaction energies of types 1—2 and 1—3. This result suggests an electrostatic origin for at least part of the error between standard model and ab initio energy surfaces. Given the range of functional forms that is used by the current generation of protein potential functions, these errors cannot be corrected by compensating for errors in other energy components. © 1995 by John Wiley & Sons, Inc.
Mono‐ and poly‐ligated complexes of Zn2+: An ab initio analysis of the metal–ligand interaction energy
Authors: Gresh Nohad , Stevens Walter J. , Krauss Morris 
Published: January 2005

AbstractDetailed investigation of the binding energetics of Zn2+ to biologically relevant model ligands has been performed by large basis set restricted Hartree‐Fock computations. This list includes neutral and anionic ligands that model the sidechains of the amino acid residues of proteins as well as those involved in binding to the metal during enzymatic activation: water, formaldehyde, formamide, imadazole, methylthiol, and the formate, hydroxyl, methoxy, methylthiolate anions. The decomposition of the intermolecular interaction energy into its components (Coulomb, exchange, polarization, and charge transfer) has been done within the frozen fragment reduced variational space procedure (RVS) developed by Stevens and Fink [W. J. Stevens and W. H. Fink, Chem. Phys. Lett., 139, 15 (1987)]. The use of the RVS procedure was dictated by the very large magnitudes of the second‐order interaction energy terms in the divalent cation complexes and the need to obtain polarization and charge‐transfer contributions in a variational sense. The behavior of the interaction energy with radial and angular variation of the approach of the metal to the ligand is explored. In addition, the nonadditive behavior of polyligated complexes is studied for water and formate. This will also provide the data for a subsequent fit to a molecular mechanics procedure that considers the second‐order interactions. © 1995 by John Wiley & Sons, Inc.
A new optimization technique for artificial neural networks applied to prediction of force constants of large molecules
Authors: Fischer Thomas H. , Petersen Wesley P. , Lüthi Hans Peter 
Published: January 2005

AbstractAn artificial neural network (ANN) method for the prediction of force constants of chemical bonds in large, polyatomic molecules was developed. The force constant information evaluated is to be used for generating accurate estimates of the Hessian used in Newton‐Raphson‐type ab initio molecular structure optimization schemes. Different network topologies as well as a training procedure based on simulated annealing are evaluated. The results show that an ANN can be designed and trained to provide force constant information within a 1.5 to 5% error band even if the range of the force constants evaluated is very large (from triple bonds to hydrogen bridges). © 1995 by John Wiley & Sons, Inc.
The molecular structures and the absorption maxima of the H‐chromophores of the indigoid dyes
Authors: Chen P. C. 
Published: January 2005

AbstractThe molecular structures of the H‐chromophore of the indigoid dyes and five other isomers are studied by ab initio MP2/6‐31 + G*//HF/6‐31 + G* method. The bond angles are affected by the π‐electron conjugation. The molecular structures of the H‐chromophores and indigoid dyes indicate that the benzene rings and the five‐membered rings are structurally important. The absorption maxima of the H‐chromophores are successfully calculated by CI‐singles‐MP2/6‐31 + G* theory for the first time and correspond to the HOMO, LUMO transition. All these transitions are the π‐π* transitions. Like the indigoid dyes, trans isomers have the bathochromic shifts of the absorption maxima, and the bathochromic shifts are found with the best donor group of NH. From these calculations, the absorption maxima of some indigoid dyes can be explained by their H‐chromophores qualitatively. © 1995 by John Wiley & Sons, Inc.
A comprehensive study of the rotational energy profiles of organic systems by ab initio MO theory, forming a basis for peptide torsional parameters
Authors: Maxwell David S. , Tirado‐Rives Julian , Jorgensen William L. 
Published: January 2005

AbstractAb initio molecular orbital calculations have been carried out on over 50 model organic molecules and ions to provide the data necessary in the determination of torsional parameters for a force field involving polypeptides. The rotational energy profiles were obtained at the HF/6‐31G*//HF/6‐31G* level. The results were supported, in many cases, by full geometry optimizations and with consideration of correlation corrections at the MP2 level. With the exception of the dihedral angle being studied, all of the molecules were fully optimized with C1 symmetry. © 1995 by John Wiley & Sons, Inc.
Toward similarity measures for macromolecular bodies: Medla test calculations for substituted benzene systems
Authors: Walker P. Duane , Mezey Paul G. 
Published: January 2005

AbstractA new method is proposed for the evaluation of numerical similarity measures for large molecules, defined in terms of their electron density (ED) distributions. The technique is based on the Molecular Electron Density Lego Assembler (MEDLA) approach, proposed earlier for the generation of ab initio quality electron densities for proteins and other macromolecules. The reliability of the approach is tested using a family of 13 substituted aromatic systems for which both standard ab initio electron density computations and the MEDLA technique are applicable. These tests also provide additional examples for evaluating the accuracy of the MEDLA technique. Electron densities for a series of 13 substituted benzenes were calculated using the standard ab initio method with STO‐3G, 3‐21G, and 6‐31G** basis sets as well as the MEDLA approach with a 6‐31G** database of electron density fragments. For each type of calculation, pairwise similarity measures of these compounds were calculated using a point‐by‐point numerical comparison of the EDs. From these results, 2D similarity maps were constructed, serving as an aid for quick visual comparisons for the entire molecular family. The MEDLA approach is shown to give virtually equivalent numerical similarity measures and similarity maps as the standard ab initio method using a 6‐31G** basis set. By contrast, significant differences are found between the standard ab initio 6‐31G** results and the standard ab initio results obtained with smaller STO‐3G and 3‐21G basis sets. These tests indicate that the MEDLA‐based similarity measures faithfully mimic the actual, standard ab initio 6‐31G** similarity measures, suggesting the MEDLA method as a reliable technique to assess the shape similarities of proteins and other macromolecules. The speed of the MEDLA computations allows rapid, pairwise comparisons of the actual EDs for a series of molecules, requiring no more computer time than other simplified, less detailed representations of molecular shape. The MEDLA method also reduces the need to store large volumes of numerical density data on disk, as these densities can be quickly recomputed when needed. For these reasons, the proposed MEDLA similarity analysis technique is likely to become a useful tool in computational drug design. © 1995 John Wiley & Sons, Inc.
Ab initio and molecular mechanics (MM2 and MM3) calculations of nonconjugated positively charged nitrogen‐containing compounds
Authors: McGaughey Georgia B. , Stewart Eugene L. , Bowen J. Phillip 
Published: January 2005

AbstractHigh‐level ab initio calculations have been performed on N‐methyl‐N‐methyleneammonium and related compounds to obtain accurate rotational barriers, structures, and vibrational frequencies. The 6‐31G** basis set has been utilized at the Hartree‐Fock level of theory for these calculations because little experimental data are available. The MM2(91) and MM3(94) force fields have been parameterized to include these nonconjugated charged nitrogen‐containing compounds. Molecular mechanics geometries and vibrational frequencies compare well with the ab initio results. © 1995 John Wiley & Sons, Inc.
Localization and quantitative evaluation of potent local binding sites on the accessible Lennard–jones surface
Authors: Cohen Alexander A. , Shatzmiller Shimon E. 
Published: January 2005

AbstractThis article presents a new method for topological analysis of molecular surfaces. Explicit representation of the van der Waals interaction according to the Lennard‐Jones potential enabled determination of the function of the maximum radius of a hypothetical atomic probe in any location, r, inside the host's domain. The size of the spatial gradient of the maximal probe's volume (named the ξ value) at that location was found to be a good descriptor of the local shape of the host. Consequently, mapping of the host domain according to the ξ value could be used as a quantitative tool for localization of potent local binding sites. The proposed method is illustrated by mapping an organic host (calix[4]arene) as well as an enzyme (HIV‐aspartic protease). Analysis of the calix[4]arene derivative revealed that the proposed method reproduces immediately the known binding site of conic calix[4]arenes. The second test case demonstrated how the catalytic site of the enzyme could be disassembled into many local binding sites. Some of these sites, located according to the proposed method, were found to follow the shape of a known inhibitor of the enzyme in a complementary manner. © 1995 John Wiley & Sons, Inc.
Calculation of molecular geometries, relative conformational energies, dipole moments, and molecular electrostatic potential fitted charges of small organic molecules of biochemical interest by density functional theory
Authors: St.‐Amant Alain , Cornell Wendy D. , Kollman Peter A. , Halgren Thomas A. 
Published: January 2005

AbstractDensity functional theory is tested on a large ensemble of model compounds containing a wide variety of functional groups to understand better its ability to reproduce experimental molecular geometries, relative conformational energies, and dipole moments. We find that gradient‐corrected density functional methods with triple‐ζ plus polarization basis sets reproduce geometries well. Most bonds tend to be approximately 0.015 Å longer than the experimental results. Bond angles are very well reproduced and most often fall within a degree of experiment. Torsions are, on average, within 4 degrees of the experimental values. For relative conformational energies, comparisons with Hartree‐Fock calculations and correlated conventional ab initio methods indicate that gradient‐corrected density functionals easily surpass the Hartree‐Fock approximation and give results which are nearly as accurate as MP2 calculations. For the 35 comparisons of conformational energies for which experimental data was available, the root mean square (rms) deviation for gradient‐corrected functionals was approximately 0.5 kcal mol−1. Without gradient corrections, the rms deviation is 0.8 kcal mol−1, which is even less accurate than the Hartree‐Fock calculations. Calculations with extended basis sets and with gradient corrections incorporated into the self‐consistent procedure generate dipole moments with an rms deviation of 5%. Dipole moments from local density functional calculations, with more modest basis sets, can be scaled down to achieve roughly the same accuracy. In this study, all density functional geometries were generated by local density functional self‐consistent calculations with gradient corrections added in a perturbative fashion. Such an approach generates results that are almost identical to the self‐consistent gradient‐corrected calculations, which require significantly more computer time. Timings on scalar and vector architectures indicate that, for moderately sized systems, our density functional implementation requires only slightly less computer resources than established Hartree‐Fock programs. However, our density functional calculations scale much better and are significantly faster than their MP2 counterparts, whose results they approach. © 1995 John Wiley & Sons, Inc.
Numerical evaluation of three‐ and four‐center bielectronic integrals using exponential‐type atomic orbitals
Authors: Cesco J. C. , Denner C. C. , Rosso A. E. , Perez J. E. , Ortiz F. S. , Contreras R. H. , Giribet C. G. , De Azúa M. C. Ruiz 
Published: January 2005

AbstractThree‐ and four‐center Slater orbital bielectronic integrals are evaluated by means of a complete function set. The method provides a series to approximate the bielectronic integrals. Their corresponding partial sums are analyzed in detail for 1s orbitals. The comparison with the Fourier transform–based method brings forth encouraging perspectives for the present approach. © 1995 John Wiley & Sons, Inc.
Calculation of relative free energy differences for the covalent hydration of organic compounds: A combined quantum mechanical and free energy perturbation study
Authors: Erion Mark D. , Reddy M. Rami 
Published: January 2005

AbstractThe relative free energy difference (ΔΔGhyd) for the reversible addition of water to two unsaturated molecules is accurately computed using a combination of ab initio quantum mechanical calculations and free energy perturbation methods. Initial attempts to calculate the absolute hydration free energy difference (ΔGhyd) for formaldehyde and trichloroacetaldehyde gave values that differed substantially from experimental results even after inclusion of electron correlation energy contributions using third‐order (MP3) and fourth‐order (MP4) Møller‐Plesset perturbation theory and QCISD(T) correlation methods at the 6‐31G** basis set level. Inaccuracies in ΔGhyd were attributed to errors in the calculation of both ΔGgas and ΔΔGsol. Gas phase quantum mechanical free energies (ΔGgas) varied significantly (2–3 kcal/mol) depending on the level of theory. Errors in ΔΔGsol were attributed to slow convergence of the calculations using the thermodynamic cycle perturbation (TCP) method with explicit solvent. These errors were minimized or canceled, however, when relative hydration free energy differences (ΔΔGhyd) were calculated using a combination of ab initio quantum mechanical calculations and free energy perturbation methods. Calculated values for a variety of aldehydes and ketones were consistent with experimental data. © 1995 John Wiley & Sons, Inc.