bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical calculations of β‐lactam antibiotics. V. AM1 calculations of hydrolysis of cephalothin in gaseous phase and influence of the solvent
Authors: Frau J. , Donoso J. , Muñoz F. , Blanco F. García 
Published: January 2005

AbstractA comprehensive study on the gas‐phase alkaline hydrolysis of cephalosporins by using the semiempirical AM1 method was carried out. Cephalothin was the model compound used on account of the presence of a good leaving group at C(3′). According to the results obtained, the hydrolysis process takes place via a twostep reaction mechanism that involves the formation of an intermediate with a fully open β‐lactam ring that still preserves the acetate group. Likewise, the exo methylene end product is chiefly formed by nucleophilic attack on the β‐lactam carbonyl group of cephalosporins containing a good leaving group at C(3′). On the other hand, the alternative mechanism involving hydrolysis of the ester function in the side chain at 3′ and subsequent hydrolysis of the resulting β‐lactam yieds essentially the corresponding enamine. The presence of a first solvation layer consisting of five water molecules showed that, even though some potential barriers are slightly increased, the mechanism involved is identical to that of the gas‐phase hydrolysis of this antibiotic. © John Wiley & Sons, Inc.
Newton–Raphson optimization of the explicitly correlated Gaussian functions for calculations of the ground state of the helium atom
Authors: Zhang Zhenghong , Kozlowski Pawel M. , Adamowicz Ludwik 
Published: January 2005

AbstractExplicitly correlated Gaussian functions have been used in variational calculations on the ground state of the helium atom. The major problem of this application, as well as in other applications of the explicitly correlated Gaussian functions to compute electronic energies of atoms and molecules, is the optimization of the nonlinear parameters involved in the variational wave function. An effective Newton–Raphson optimization procedure is proposed based on analytic first and second derivatives of the variational functional with respect to the Gaussian exponents. The algorithm of the method and its computational implementation is described. The application of the method to the helium atom shows that the Newton–Raphson procedure leads to a good convergence of the optimization process. © 1994 by John Wiley & Sons, Inc.
Semiempirical study of compounds with intramolecular OH…︁O hydrogen bonds. II. Further verification of a modified MNDO method
Authors: Rodríguez Jesús 
Published: January 2005

AbstractIn the forerunner of this article, we described a MNDO modification designed for studies of compounds with intramolecular OH…︁O hydrogen bonds. Here, we report the further verification of the modification by means of its application to 14 compounds not considered in its development. Comparison of the calculated structural parameters and proton transfer characteristics with available experimental or ab initio results, and with those obtained using MNDO, AM1, MNDO/H, MNDO/M, and PM3, supports the validity of the new modification for prediction of hydrogen bond characteristics. © 1994 by John Wiley & Sons, Inc.
A ring‐bracing approach to computer‐assisted ligand design
Authors: Leach Andrew R. , Lewis Richard A. 
Published: January 2005

AbstractRigid inhibitors suffer a smaller loss of conformational entropy when they bind to a macromolecular receptor than their acyclic counterparts. They can also be useful for elucidating pharmacophores due to their reduced conformational space and may be more amenable to synthesis. Computational approaches to rational drug design should therefore take these factors into consideration when suggesting possible compounds. We describe how an acyclic chain which links two parts of a receptor site can be ‘braced’ using ring templates. The acyclic chains may be produced from a number of sources, including lattices or the structures of known inhibitors. The resulting structures contain a rich variety of isolated and fused ring systems, which provide many useful molecular skeletons for subsequent inhibitor design. © 1994 by John Wiley & Sons, Inc.
Quantum mechanical computations on very large molecular systems: The local self‐consistent field method
Authors: Théry Vincent , Rinaldi Daniel , Rivail Jean‐Louis , Maigret Bernard , Ferenczy György G. 
Published: January 2005

AbstractQuantum chemical computations on a subset of a large molecule can be performed, at the neglect of diatomic differential overlap (NDDO) level, without further approximation provided that the atomic orbitals of the frontier atoms are replaced by parametrized orthogonal hybrid orbitals. The electrostatic interaction with the rest of the molecule, treated classically by the usual molecular mechanical approximations, is included into the self‐consistent field (SCF) equations. The first and second derivatives of energy are obtained analytically, allowing the search for energy minima and transition states as well as the resolution of Newton equations in molecular dynamics simulations. The local self‐consistent field (LSCF) method based on these approximations is tested by studying the intramolecular proton transfer in a Gly‐Arg‐Glu‐Gly model tetrapeptide, which reveals an excellent agreement between a computation performed on the whole molecule and the results obtained by the present method, especially if the quantum subsystem includes the side chains and the peptidic unit in between. The merits of the LSCF method are examplified by a study of proton transfer in the Asp69—Arg71 salt bridge in dihydrofolate reductase. Simulations of large systems, involving local changes of electronic structure, are therefore possible at a good degree of approximation by introducing a quantum chemical part in molecular dynamics studies. This methodology is expected to be very useful for reactivity studies in biomolecules or at the surface of covalent solids. © 1994 by John Wiley & Sons, Inc.
Theoretical analysis of the role of the solvent on the reaction mechanisms: One‐step versus two‐step ketene–imine cycloaddition
Authors: Assfeld X. , Ruiz–lopez M. F. , Gonzalez J. , Lopez R. , Sordo J. A. , Sordo T. L. 
Published: January 2005

AbstractThe effect of correlation energy, basis set size, zero‐point energy (ZPE) correction, and solvation on the reaction mechanism of the ketene–imine cycloaddition reaction has been investigated. The electrostatic solvent effect was studied with a self‐consistent reaction field method in which the solvation energy is obtained using a multipole expansion of the molecular charge distribution. The ab initio results have been analyzed by means of a theoretical method based on the expansion of the MOs of the supermolecule in terms of those of the reactants and the performance of the configuration analysis. In gas phase, due to the correlation energy and/or the ZPE corrections, the reaction is predicted to be a one‐step process. In solution, the stabilization of the charge‐transferred configurations results in the occurrence of a very stable, Zwitterionic intermediate giving a two‐step mechanism. © 1994 by John Wiley & Sons, Inc.
New approach to the semiempirical calculation of atomic charges for polypeptides and large molecular systems
Authors: Sternberg Ulrich , Koch Frank–thomas , Möllhoff Margit 
Published: January 2005

AbstractStarting from the bond polarization theory (BPT), a new semiempirical method for the calculation of net atomic charges is developed. The bond polarization theory establishes a linear dependence of atomic charges from the bond polarization energy. This energy is calculated from the hybrid orbitals forming a bond and the point charges within the neighborhood. Empirical parameters are introduced for the polarity of an unpolarized bond and for the change of the atomic charge with σ‐ and π‐bond polarization. Because these parameters are linear, they can be calibrated directly using net atomic charges from ab initio calculations. This procedure was performed using the charges from STO3G calculations on a set of 18 amino acids. Using the two parameters for CH, OH, σ‐CO, and NH bonds and the three parameters for CC, CO, and CN bonds, the 350 ab initio charges can be reproduced with high accuracy by solving sets of linear equations for the charges. The calculation of charges for large molecular systems including all inter‐ and intramolecular mutual polarizations requires only a few seconds (up to 100 atoms) or minutes (700 atoms) on a PC. This procedure is well suited for the application in molecular mechanics or molecular dynamics programs to overcome the limitations of most force fields used up to now. One of the weakest points in these programs is the use of fixed or topological charges to define the electrostatic potential. As an application of the new method, we calculated the interaction energy of an ion with valinomycin. This ring molecule forms octahedral oxygen cages around ions like potassium and acts thereby as selective ion carrier. To accomplish this function, valinomycin has to strip off the hydratization spheres of the ions, and therefore its preference for certain types of ions could be deduced from the interaction energies. © 1994 by John Wiley & Sons, Inc.
A truncated Newton minimizer adapted for CHARMM and biomolecular applications
Authors: Derreumaux Philippe , Zhang Guihua , Schlick Tamar , Brooks Bernard 
Published: January 2005

AbstractWe report the adaptation of the truncated Newton minimization package TNPACK for CHARMM and biomolecular energy minimization. TNPACK is based on the preconditioned linear conjugate–gradient technique for solving the Newton equations. The structure of the problem—sparsity of the Hessian—is exploited for preconditioning. Experience with the new version of TNPACK is presented on a series of molecular systems of biological and numerical interest: alanine dipeptide (N‐methyl‐alanyl‐acetamide), a dimer of N‐methyl‐acetamide, deca‐alanine, mellitin (26 residues), avian pancreatic polypeptide (36 residues), rubredoxin (52 residues), bovine pancreatic trypsin inhibitor (58 residues), a dimer of insulin (99 residues), and lysozyme (130 residues). Detailed comparisons among the minimization algorithms available in CHARMM, particularly those used for large‐scale problems, are presented along with new mathematical developments in TNPACK. The new TNPACK version performs significantly better than ABNR, the most competitive minimizer in CHARMM, for all systems tested in terms of CPU time when curvature information (Hessian/vector product) is calculated by a finite‐difference of gradients (the numeric option of TNPACK). The remaining derivative quantities are, however, evaluated analytically in TNPACK. The CPU gain is 50% or more (speedup factors of 1.5 to 2.5) for the largest molecular systems tested and even greater for smaller systems (CPU factors of 1 to 4 for small systems and 1 to 5 for medium systems). TNPACK uses curvature information to escape from undesired configurational regions and to ensure the identification of true local minima. It converges rapidly once a convex region is reached and achieves very low final gradient norms, such as of order 10−8, with little additional work. Even greater overall CPU gains are expected for large‐scale minimization problems by making the architectures of CHARMM and TNPACK more compatible with respect to the second‐derivative calculations. © 1994 by John Wiley & Sons, Inc.
Analysis of the ring‐form tautomers of psicose with MM3 (92)
Authors: French Alfred D. , Dowd Michael K. 
Published: January 2005

AbstractBy nuclear magnetic resonance (NMR), the four ring forms of psicose, α‐and β‐pyranose and α‐ and β‐furanose, have almost equal concentrations in aqueous solution. Prediction of this equilibrium by molecular mechanics tests both the balance within the force field and the methods for including the many degrees of freedom in the system. For both the α‐ and β‐furanoses, each of 410 different ring shapes was studied in combination with 37 combinations of staggered side‐group orientations. Of these, 48 and 57 initial combinations of side‐group orientations contributed to the α‐ and β‐furanose energy surfaces. The pyranoses were analyzed in two steps. First, the 38 characteristic ring conformations were optimized with the 63 staggered side‐group combinations. All combinations that gave the lowest energy at one or more of the 38 shapes (20 combinations for α‐pyranose, 15 for β‐pyranose) were then optimized with 4912 different ring forms. Ring conformations were generated by fixing nonadjacent ring atoms (two for furanose rings, three for pyranoses) at increments of 0.1 Å from the plane of the remaining three atoms. At a dielectric constant of 4.0, prediction was in fair agreement with the NMR results. Model northern and southern conformers contribute to the furanose equilibrium, and both chairs are important for α‐psicopyranose. © 1994 by John Wiley & Sons, Inc.
Thermodynamic integration calculations on the relative free energies of complex ions in aqueous solution: Application to ligands of dihydrofolate reductase
Authors: Cummins Peter L. , Gready Jill E. 
Published: January 2005

AbstractMolecular dynamics (MD) simulation and thermodynamic integration (TI) techniques have been used to study the relative free energies of the 8‐methyl‐N5‐deazapterin and 8‐methyl‐pterin cations (N3 protonated) in aqueous solution. The MD simulations were performed at constant temperature and volume, and the mutations between the cations were carried out by changing the coupling parameter continuously and linearly with the MD simulation time (continuous coupling or slow growth method). The free energy changes have been calculated using both linear and nonlinear couplings of the potential energy functions. Free energy changes have also been computed using the perturbation method for comparison. After separation into electrostatic and van der Waals mutations, most (ca. 80%) of the total free energy change is found to be due to mutation of the electrostatic terms. The free energy change is found to be sensitive to the cutoff radii for interactions between solvent molecules, but rather insensitive to the cutoff radii for interactions between cation and solvent. The free energy changes have also been calculated using various cation and solvent models. Atomic charges for the cations were derived from the molecular electrostatic potential at the semiempirical AM1 and ab initio self‐consistent field (SCF) (3‐21G, 6‐31G, 6‐31G*, 6‐311G**) levels using AM1 and 3‐21G optimized geometries. The TIP3P and SPC models were adopted for the solvent. For the TIP3P solvent model, the order of the free energy change is 6‐31G > 3‐21G > 6‐31G* ≈ 6‐311G** > AM1, where the difference between 6‐31G and AM1 is approximately 1 kcal/mol. The free energies obtained using 3‐21G optimized geometries are approximately 0.7 kcal/mol larger than those obtained using AM1 geometries for the cations. The free energy change computed using the TIP3P/6‐311G* model is 0.3 kcal/mol larger than that obtained for the SPC/6‐311G* model. © 1994 by John Wiley & Sons, Inc.
Failure of net atomic charge models to represent the van der Waals envelope electric potential of n‐alkanes
Authors: Williams Donald E. 
Published: January 2005

AbstractTraditional net atomic charge models were found unsatisfactory for representing the molecular electric potential (MEP) of n‐alkanes ethane through decane in their van der Waals envelopes. The MEP of these molecules was calculated by ab initio methods. Mulliken atomic charges were erratic and gave root mean square (rms) relative errors of fit to the MEP ranging from 152 to 607% with the 6‐31 + + g** basis set. Fitting the MEP with potential‐derived net atomic charges (PD charges) gave errors ranging from 51 to 62% with the same basis set. The use of larger basis sets, inclusion of electron correlation, use of more MEP data points, or relaxation to optimal structural geometry did not improve significantly the representation of the MEP by net atomic charges. In many cases PD charges of hydrogen atoms were negative, and carbon atoms were positive. To improve the representation of the MEP of n‐alkanes, augmentation of the model with nonatomic sites was investigated with the program PDM93. Models with additional charge sites located between hydrogens, on a line bisecting the CH2 group, achieved fits to the MEP with errors reduced to 8% or less, except for n‐butane, where the fitting error was 16%. The PD models augmented with methylene bisector sites generally show positive hydrogen charges. They also show CH2 group charge alternation along the n‐alkane chains. The augmented charge models were consistent with the observed quadrupole moment of ethane and gave satisfactory predictions for the crystal structures of pentane and octane. © 1994 by John Wiley & Sons, Inc.
Principal component analysis of dipeptides
Authors: Susnow Roberta , Schutt Clarence , Rabitz Herschel 
Published: January 2005

AbstractPrincipal component analysis applied to a set of dipeptides illustrates how changes in families of parameters act in concert to produce overall molecular structural changes. Principal component analysis is an eigenvalue–eigenvector analysis whereby the parametric sensitivity coefficient matrix is manipulated to produce weighted principal components, which reveal the variant and invariant directions in the parameter space. This analysis summarizes the sensitivity results by revealing interdependence among the parameter values with regard to their role in controlling the molecular structure. An analysis of the principal components reveals hidden relationships among the parameters. Thus, those parameters, which were thought to be of controlling significance with respect to the molecular structure, may, in fact, not be (or vice versa) due to cooperative parametric interactions; as a result, the parameters of significance in a sequence of dipeptides are identified. In general, for the dipeptides studied, there is mutual exclusion of dominant parameters between the sets of invariant and variant eigenvectors. © 1994 by John Wiley & Sons, Inc.
Structural and electronic property changes of the nucleic acid bases upon base pair formation
Authors: Santamaria R. , Vázquez A. 
Published: January 2005

AbstractA systematic study of structures and electronic properties has been carried out for the nucleic acid bases adenine, guanine, thymine, and cytosine and for the base pairs adenine–thymine and guanine–cytosine. We focus our attention on these properties, which experience significant changes when single nucleic bases join to form base pairs. Such properties are expected to play an important role during the formation of the DNA molecule in its B conformation. All‐electron calculations with inclusion of correlation effects were performed according to the local and nonlocal density functional approaches. We compare our results with previous ab initio and semiempirical values and with available experimental data. Advantages and disadvantages for these density functional‐based methods are discussed. We conclude that applications of such models to investigate larger compounds of a similar nature are promising. © 1994 by John Wiley & Sons, Inc.
Incorporation of bond‐length constraints in Monte Carlo simulations of cyclic and linear molecules: Conformational sampling for cyclic alkanes as test systems
Authors: Pertsin Alexander J. , Hahn Jutta , Grossmann Hans P. 
Published: January 2005

AbstractA simple method for incorporating bond‐length constraints in Monte Carlo simulations of cyclic and linear molecules is described. As an example, the conformational behavior of five even‐numbered cyclic alkanes is studied using Monte Carlo simulation and the MM2 force field. © 1994 by John Wiley & Sons, Inc.
Thermodynamic molecular mechanics force field: Modified QCFF program
Authors: Kar Mangalya , Lenz Terry G. , Vaughan John D. 
Published: January 2005

AbstractThe QCFF program originated by Warshel and Karplus4a was modified to compute accurate thermodynamic properties So, C, (H – H)/T, and ΔH for various acyclic and cyclic alkenes and alkadienes. Modifications consisted of adjusted bond angle, dihedral angle, bond stretch, and bond energy parameters that improved calculated vibrational frequencies, zero point energies, and thermodynamic functions. Supplemental torsional potential energy functions that were added to existing torsional functions led to greatly improved relative conformer energies and ΔH values. It was shown that inclusion of hindered internal rotation leads to significantly better agreement of calculated thermodynamic functions with observed values for acyclic alkenes at high temperatures. The calculated thermodynamic properties of the alkenes and alkadienes were deemed sufficiently accurate for calculation of standard enthalpies and Gibbs free energies of gas phase chemical reactions at various temperatures. © 1994 by John Wiley & Sons, Inc.
Linear dependency in the refinement of force constants with the Jacobian method
Authors: Ganda‐Kesuma Fransiska S. , Miller Kenneth J. 
Published: January 2005

AbstractThe Jacobian method in the refinement of force constants is studied. Theoretical and experimental frequencies and other observables, νs, are matched by minimizing ΣsWs(ν – ν)2, where s = 1, 2, 3,…, proceeds over all normal modes and isotopes, and Ws are weighting factors. Modification of the theoretical frequencies is accomplished with the Jacobian matrix, J, with elements Jsi = ∂νs/∂ki involving each force constant or associated parameter, ki, i = 1, 2, 3,…, by Δν = JΔk. The parameters are adjusted directly with Δk = (JTWJ)−1(JW) Δν, where W is a diagonal matrix which weights the frequencies. The linear dependence problem must be addressed prior to inversion of JTWJ. The approach entails diagonalization of JT WJ, analysis of the components of the eigenvectors associated with zero and small eigenvalues, identification of the linearly dependent parameters, successive elimination of selective parameters, and a repeat of this procedure until linear dependency is removed. The Jacobian matrices are obtained by differencing the frequencies when the parameters are varied and by numerical and analytical evaluation of the derivative of the potential. The unitary transformation, U, used to calculate J = UT (∂F/∂k)U or J = UT (ΔF/Δk)U, is obtained from the diagonalization of the Hessian, Fmn = ∂2ν/∂pm∂qn, where p, q = x, y, z are the Cartesian coordinates for atoms m, n = 1, 2, 3,…, at the initial value of ki, i = 1, 2, 3, ⃜ The accuracy of and the ability to evaluate the Jacobian matrix by these methods are discussed. Applications to CH4, H2CO, C2H4, and C2H6 are presented. Linearly dependent and ill‐conditioned parameters are identified and removed. The procedure is general for any observable quantity. © 1994 by John Wiley & Sons, Inc.