bluuebunny/crossref_metadata_2025 huggingface dataset:
Vectorizable algorithm for green function and many‐body perturbation methods
Authors: Zakrzewski Vyacheslav G. , von Niessen Wolfgang
Published: January 2005

The principles of an efficient, fast algorithm for the calculation of diagrams appearing in Green function and many‐body perturbation methods are discussed and timing examples are given. Within the suggested algorithm, the third order‐diagrams required in the Green function approach are evaluated by arranging computations in such a way that the most inner loops contain only simple scalar products and multiplication of vector by scalar operations. The molecular symmetry is taken into account for abelian groups. © 1993 John Wiley & Sons, Inc.
Use of effective core potentials forab initiocalculations on molecular siloxanes and silicates
Authors: Earley Clarke W.
Published: January 2005

A series ofab initioelectronic structure calculations have been performed on the (H3Si)2O molecule using a range of basis sets. The accuracy of these calculations was evaluated by comparison with several experimental measurements. These calculations support earlier results indicating that polarization functions on the bridging oxygen atom are usually required to obtain a bent geometry for the Si‐O‐Si linkage in disiloxane. It was found thatab initiocalculations utilizing effective core potentials and a double‐ζ valence description augmented with polarization functions (CEP‐31G*) provide results comparable in quality to those obtained using the all‐electron 6‐31G* basis set. To demonstrate the general utility of these effective core potential basis sets for theoretical studies of molecular silicates, calculations were performed on the (HO)3SiOSi(OH)3molecule. The results obtained are in excellent agreement with previous experimental andab initiocalculations using all‐electron basis sets. © 1993 John Wiley & Sons, Inc.
Is tetrahedral H42+ a minimum? Anomalous behavior of popular basis sets with the standard p exponents on hydrogen
Authors: Glukhovtsev Mikhail N. , Schleyer Paul Von Ragué , van Eikema Hommes Nicolaas J.R. , De M. Carneiro Jose Walkimar , Koch Wolfram
Published: January 2005

The nature of the tetrahedral H42+ stationary point (minimum or triply degenerate saddle) depends remarkably upon the theoretical level employed. Harmonic vibrational analyses with, e.g., the 6‐31G** (and 6‐31 + +G**) and Dunning's [4s2p1d;2s1p] [D95(d,p)] basis sets using the standard p exponent suggest (erroneously) that the Td geometry is a minimum at both the HF and MP2 levels. This is not the case at definitive higher levels. The C3H42+ structure with an apical H is another example of the failure of the calculations with the 6‐31G**, 6‐311G**, and D95(d,p) basis sets. Even at MP2/6‐31G** and MP2/ cc‐pVDZ levels, the C3v structure has no negative eigenvalues of the Hessian. Actually, this form is a second‐order saddle point as shown by the MP2/6‐31G** calculation with the optimized exponent. The D4h methane dication structure is also an example of the misleading performance of the 6‐31G** basis set. In all these cases, energy‐optimized hydrogen p exponents give the correct results, i.e., those found with more extended treatments. Optimized values of the hydrogen polarization function exponents eliminate these defects in 6‐31G** calculations. Species with higher coordinate hydrogens may also be calculated reliably by using more than one set of p functions on hydrogen [e.g., the 6‐31G(d,2p) basis set]. Not all cases are critical. A survey of examples, also including some boron compounds, provides calibration. © 1993 John Wiley & Sons, Inc.
Rapid approximation to molecular surface area via the use of Boolean logic and look‐up tables
Authors: Le Grand Scott M. , Merz Kenneth M.
Published: January 2005

We report the development of a new approximate method of calculating molecular surface areas. Our technique is based upon the method of Sharake and Rupley but incorporates several major advances. First, we represent the state of surface points as bits in a bit string so we can utilize Boolean operations to simultaneously turn off multiple test points in one Boolean AND operation. Second, we use a series of Boolean mask look‐up tables to reduce the time complexity of the calculation of molecular surface area down to the same magnitude as doing a potential energy evaluation. When we use a 256 surface point sphere for all of the atoms in BPTI, a 454 nonhydrogen atom protein, and a 1.4‐Å solvent probe, we in general underestimate the total solvent‐accessible surface area (SASA) by approximately 1.25% with a correlation coefficient of 0.9990 over a wide range of conformations. The average CPU time required to calculate the SASA of a BPTI conformer is 0.58 s on an SGI 4D/220 workstation. We also describe a method by which we can calculate an approximate finite difference SASA gradient for BPTI in 0.79 of CPU time. © 1993 John Wiley & Sons, Inc.
Molecular orbital studies of enzyme mechanisms. II. Catalytic oxidation of alcohols by liver alcohol dehydrogenase
Authors: von Onciul Andreas Ritter , Clark Timothy
Published: January 2005

Semiempirical (AM1) molecular orbital theory has been used to investigate the oxidation of alcohols at the active site of liver alcohol dehydrogenase (LADH). The model active site consists of a zinc dication coordinated to two methyl‐mercaptans (Cys‐46, Cys‐176), an imidazole (His‐67), and a water. An imidazole (His‐51) hydrogen bonded to a hydroxy‐acetate (Ser‐48) forms the remote base. AM1 calculations that address the two distinct steps in the catalytic mechanism of ethanol oxidation by LADH are reported. These two steps are: (1) the deprotonation of ethanol by imidazole (His‐51) via hydrogen‐bonded hydroxy‐acetate (Ser‐48), creating a proton relay system; and (2) the rate‐limiting hydride transfer step from ethanol C1 to nicotinamide adenine dinucleotide (NAD+), leading to product formation. Detailed calculations have been used to resolve the unsolved problems of mechanisms that have been suggested on the basis of kinetic data and crystal structures of several LADH complexes. We investigated two possible mechanisms for the deprotonation of ethanol, by zinc‐bound OH− and by direct deprotonation of zinc‐bound ethanol by imidazole via hydroxyacetate (Ser‐48). Our calculations show that there is no need for LADH to activate a water molecule at the active site as in many other zinc enzymes. This result agrees with experimental evidence. Our calculations also indicate that substrates are bound in an inner‐sphere‐pentacoordinated complex to the active site zincion. In this case, spectroscopic investigations agree with our results but crystallographic data do not. The highest activation energy is found for the hydride transfer, in agreement with the experiment. Finally, we proposed an alternative mechanism for the mode of action of LADH based upon our results. © 1993 John Wiley & Sons, Inc.
Prediction of possible crystal structures for C‐, H‐, N‐, O‐, and F‐containing organic compounds
Authors: Holden James R. , Du Zuyue , Ammon Herman L.
Published: January 2005

A procedure is reported for the prediction of dense crystal structures of C‐, H‐, N‐, O‐, and F‐containing organic compounds in the primitive triclinic, monoclinic, and orthorhombic space groups with Z ≤ 4. The crystal environments of molecules in 242 crystal structures have been analyzed to determine the common coordination sphere pattens. This led to the development of the MOLPAK (MOLecular PAcKing) program, which uses a rigid‐body molecular structure probe to build packing arrangements (possible crystal structures) in the various space groups. A MOLPAK search, which involves the investigation of all unique orientations of a central molecule and the construction of the appropriate coordination patterns about the central molecule, provides a 3‐D map of minimum unit cell volume as a function of the orientation of the central molecule. MOLPAK uses a repulsion‐only potential and a preset threshold to place molecules in contact with each other. The 5–10 smallest volume packing arrangements from a search are subjected to a lattice energy minimization refinement with the WMIN program to yield possible crystal structures. The results are described from the analyses of several known compounds starting with the crystal molecular structures as the MOLPAK search probes in the P1, P21, P21/c, and P212121 space groups. In addition, several examples are given in which the search probes were created by AM1 geometry optimization of preliminary molecular models. More extensive data are given in supplementary tables. © 1993 John Wiley & Sons, Inc.
The ethylene group as a peptide bond mimicking unit: A theoretical conformational analysis
Authors: Bagińki Maciej , Piela Lucjan , Skolnick Jeffrey
Published: January 2005

One of the features of the polypeptide backbone is that it represents a flexible chain that contains almost rigid CONH peptide bonds. One may try to substitute one or more such bonds by another relatively rigid unit to maintain the overall conformational properties of the backbone and at the same time modify some other properties of the molecule (“pseudopeptide”), such as the ability to form hydrogen bonds. By a detailed conformational analysis, it is shown that the carboncarbon double bond is quite isosteric with the peptide bond and for this reason suitable for such a substitution. This is accomplished by applying molecular mechanics in calculation of the ϕ, ψ maps for pseudopeptide analogs of the N‐acetyl‐Ala‐NHMe molecule. © 1993 John Wiley & Sons, Inc.
Finite element approach to the electrostatics of macromolecules with arbitrary geometries
Authors: You Tony J. , Harvey Stephen C.
Published: January 2005

A new treatment of macromolecular electrostatics has been developed using the 3‐D finite element method to numerically solve the linear Poisson–Boltzmann equation. The procedure is based upon a model where the macromolecule is represented at an atomic level of detail, while the solvent is treated in a continuum approximation. The finite element method has two major advantages over previous methods based upon the finite difference approach. First, charges are located on atomic centers rather than being distributed onto grid points. Second, an isoparameter model allows the use of noncubic grids, providing a more accurate description of molecular shape. The principal disadvantage of the finite element method has been its computational complexity, which arises from the use of large matrices. To overcome this difficulty, a new matrix representation has been formulated and an iterative solution procedure has been adopted. The combination of these two techniques drastically reduces the size of the system matrix and increases the overall computational efficiency of the algorithm, making the new treatment computationally competitive with the finite difference approach. Because of the mathematical rigor and physical sophistication of the finite element algorithm, the new treatment is able to give an accurate description of the electrostatic potential distribution in a macromolecular system. Results on test cases with simple geometries show that the new treatment is able to reach the same level of accuracy achieved by the finite difference method while using a lower grid density. Near changes and surfaces, our method is more accurate than the finite difference method. The overall maximum deviation between computed and analytic potentials is less than 3% except in regions surrounding charges. The applicaions of both the finite element and finite difference methods to the same biomolecular systems produce similar potential distributions that would become identical in the limit of infinitely fine grids. © 1993 John Wiley & Sons, Inc.
Study of localized molecular orbitals using group theory methods and its approach to the many‐electron correlation problem. III. Orthogonal bonded functions
Authors: Zhou Taijin
Published: January 2005

By using the group symmetrical localized molecular orbitals (SLMOs) as configuration‐generating orbitals (CGOs) of many‐electron wave functions, the symmetry adaptation of many‐electron spaces is greatly simplified, and novel orthogonal bonded functions (OBFs), as complete space‐ and spin‐adapted antisymmetrized products, are introduced. The corresponding programs for the solutions of OBFs are developed. © 1993 John Wiley & Sons, Inc.
Are most of the stationary points in a molecular association minima? Application of Fraga's potential to benzene–benzene
Authors: Rubio Mercedes , Torrens Francisco , Sánchez‐Marín José
Published: January 2005

The importance of characterizing the stationary points of the intermolecular potential by means of Hessian eigenvalues is illustrated for the calculation of the benzene–benzene interaction using an atom‐to‐atom pair potential proposed by Fraga (FAAP). Two models, the standard one‐center‐per atom and another using three‐centers‐per atom due to Hunter and Sanders, are used to evaluate the electrostatic contributions and the results are compared. It is found in both cases that although using low‐gradient thresholds allows optimization procedures to avoid many stationary points that are not true minima computing time considerations makes the usual procedure of using high‐gradient thresholds [say, 10−2 kj/(mol Å)] as the most efficient. Moreover, this later procedure can be recommended because the actual minima can be characterized by means of Hessian eigenvalues even if these high‐gradient thresholds are used, and further decreasing of the convergence criterion does not imply significant modifications in the geometric parameters of the minima. The possible advantages of using the three‐centers‐per‐atom model for the calculation of molecular associations between delocalized systems are also discussed on the basis of the agreement of the benzene–benzene results with experimental and theoretical data taken from the literature. © 1993 John Wiley & Sons, Inc.
Torsional flexing: Conformational searching of cyclic molecules in biased internal coordinate space
Authors: Kolossváry István , Guida Wayne C.
Published: January 2005

A new stochastic (Monte Carlo) procedure, termed torsional flexing, has been devised for searching the conformational space of cyclic molecules. Torsional flexing causes a local, torsion angle‐biased, distortion of a ring bond in a cyclic molecule. Because torsional flexing does not cause large atomic movements, even when it is applied to several bonds simultaneously, subsequent energy minimization generally proceeds rapidly. Nevertheless, the torsional flexing method is prone to generate structures that cross energy barriers so that the structure resulting after energy minimization is frequently a different conformer of the cyclic molecule. Conformational searches on cycloheptadecane, oxobrefeldin A, cyclopenta‐L‐alanine, and rifamycin SV based upon torsional flexing indicated that torsional flexing is among the best methods yet devised for searching the conformational space of flexible cyclic molecules. © 1993 John Wiley & Sons, Inc.
Molecular dynamics simulation of cellobiose in water
Authors: Hardy B.J. , Sarko A.
Published: January 2005

The conformational behavior of cellobiose was studied by molecular dynamics simulation in a periodic box of waters. Several different initial conformations were used and the results compared with equivalent vacuum simulations. The average positions and rms fluctuations within single torsional conformations of cellobiose were affected only slightly by the solvent. However, water damped local torsional librations and transitions. The conformational energies of the solute and their fluctuations were also sensitive to the presence of solvent. Intramolecular hydrogen bonding was weakened relative to that observed in vacuo due to competition with solvating waters. All cellobiose hydroxyl groups participated in intermolecular hydrogen bonds with water, with approximately eight hydrogen bonds formed per glucose ring. The hydrogen bonding was predominantly between water hydrogens and solute hydroxyl oxygens. Intermolecular hydrogen bonding to ring and bridge oxygens was seldom present. The diffusion coefficients of both water and solute agree closely with experimental values. Water interchanged rapidly between the solvating first shell and the bulk on the picosecond time scale. © 1993 John Wiley & Sons, Inc.
Semidirect MP2 gradient evaluation on workstation computers: The MPGRAD program
Authors: Haase Frank , Ahlrichs Reinhart
Published: January 2005

A semidirect implementation of the closed‐shell MP2 gradient for efficient use on workstation computers is presented. The approach is based on the algorithm proposed by Frisch and coworkers but includes several modifications to reduce disk storage requirements and exploits nonabelian point group symmetry. The performance of the resulting program MPGRAD (BIOSYM Corp., San Diego, CA) is demonstrated in applications to the molecules [AlSi(CH3)3]4 and ferrocene. The largest calculation involved 492 basis functions and was carried out on IBM RS/6000 workstations with memory sizes of 32 and 128 Mb. The ratio of CPU to wallclock time exceeds 90% in all typical applications. © 1993 John Wiley & Sons, Inc.
Techniques for geometry optimization: A comparison of cartesian and natural internal coordinates
Authors: Baker Jon
Published: January 2005

A comparison is made between geometry optimization in Cartesian coordinates, using an appropriate initial Hessian, and natural internal coordinates. Results on 33 different molecules covering a wide range of symmetries and structural types demonstrate that both coordinate systems are of comparable efficiency. There is a marked tendency for natural internals to converge to global minima whereas Cartesian optimizations converge to the local minimum closest to the starting geometry. Because they can now be generated automatically from input Cartesians, natural internals are to be preferred over Z‐matrix coordinates. General optimization strategies using internal coordinates and/or Cartesians are discussed for both unconstrained and constrained optimization. © John Wiley & Sons, Inc.
CONCEPTS: New dynamic algorithm for de novo drug suggestion
Authors: Pearlman David A. , Murcko Mark A.
Published: January 2005

We describe a new method for de novo design of molecules that bind to protein active sites. The method, CONCEPTS (Creation of Novel Compounds by Evaluation of Particles at Target Sites), places a group of atom‐like particles in the site. The particles are free to move within the site to improve binding to the protein. A key innovation of this technique is that covalent connections are made among the particles in a stochastic and dynamically reversible manner. These changes in the topology are either accepted or rejected depending on their ability to improve the total energy of the enzyme–inhibitor complex. The method is applied to two test systems: The FK506 binding protein (FKBP‐12) and HIV‐1 aspartyl protease. In both cases, we are able to predict, de novo, drugs that have striking similarities to known potent inhibitors and that can successfully be used to generate “hits” of the known inhibitors from a data base. © John Wiley & Sons, Inc.
Ab initio molecular orbital calculations for 3,6‐dihydro‐1,2‐dithiin and 3,6‐dihydro‐1,2‐dioxin
Authors: Po Henry N. , Freeman Fillmore , Lee Choonsun , Hehre Warren J.
Published: January 2005

Optimized geometries and total energies for the conformers of 3,6‐dihydro‐1,2‐dithiin (2) and 3,6‐dihydro‐1,2‐dioxin (3) were calculated at several ab initio MO levels: RHF/3‐21G(*), RHF/6‐31G*, MP2/6‐31G*, and MP2/6‐31G*/ /RHF/3‐21G(*). For the dioxin, in addition to the above levels the corresponding nonextended basis sets ab initio methods were also carried out. The dithiin results are compared with those of simple disulfanes, HSSH and (CH3)2S2, whose optimized geometries agree closely with the observed structures, which is the gauche (C2 symmetry). For the disulfanes, the gauche geometries from RHF/3‐21G(*) are in good agreement with the observed structure while the RHF/3‐21G results best fit the dioxin. Pertinent structural data at the RHF/3‐21G(*) for the half‐chair (C2) dithiin are: bond lengths, SS, CS, CC, and CC, 2.050, 1.817, 1.515, and 1.317 Å, respectively; bond angles, CSS, CCS, and CCS, 98.0, 114.2, and 127.8°, respectively; CSSC dihedral angle of 63.2°; and twist angle of 36.5°. The total energy for half‐chair dithiin at MP2/6‐31G*//RHF/3‐21G(*) is less than the planar (C2v) and the half‐boat (Cs) structures by 69.67 and 29.05 kJ/mol, respectively. The calculated structural data (vs. observed) at RHF/3‐21G for the half‐chair dioxin are: bond lengths, OO, CO, CC, and CC, 1.464 (1.463), 1.454, 1.509, and 1.313 Å (1.338 Å), respectively; bond angles, COO, CCO, and CCO, 105.0, 109.8 (110.3), and 120.7° (119.9°), respectively; COOC dihedral angle of 79.7° (80 ± 2°); and twist angle of 39.0 (38.3°). The total energy for half‐chair dioxin at MP2/6‐31G//RHF/3‐21G is less than the planar and the half‐boat structures by 70.35 and 42.85 kJ/mol, respectively. The total energies calculated at the extended basis sets (*) ab initio levels for the C2 symmetry dioxin are much lower than those of the nonextended basis sets. © John Wiley & Sons, Inc.
Distributed data parallel coupled‐cluster algorithm: Application to the 2‐hydroxypyridine/2‐pyridone tautomerism
Authors: Rendell Alistair P. , Guest Martyn F. , Kendall Rick A.
Published: January 2005

The recently developed parallel coupled‐cluster algorithm of Rendell, Lee, and Lindh [Chem. Phys. Lett., 194, 84 (1992)] is extended to allow four‐indexed quantities containing one or two indices in the virtual orbital space to be stored across the global memory of distributed‐memory parallel processors. Quantities such as the double‐excitation amplitudes can now be distributed over multiple nodes, with blocks of data retrieved from remote nodes by the use of interrupt handlers. As an application of the new code, we have investigated the potential energy surface of the 2‐hydroxypyridine/2‐pyridone tautomers. Using large basis sets, the structure of each tautomer and the transition state connecting the two minima has been determined at the SCF level. The relative energy difference and the activation energy were then redetermined using the MP2, CCSD, and CCSD(T) methods. All calculations have been performed on Intel distributed‐memory supercomputers. The largest coupled‐cluster calculations contained over 2 million double‐excitation amplitudes. © John Wiley & Sons, Inc.
Electric dipole polarity of diatomic molecules
Authors: Huzinaga S. , Miyoshi E. , Sekiya M.
Published: January 2005

The restricted SCF (single‐configuration SCF) and MCSCF (multiconfiguration SCF) calculations are performed to compute the ground‐state electric dipole moments of four pairs of diatomic molecules—(1) CO and BF; (2) SiO and AlF; (3) CS and BCl; and (4) SiS and AlCl—at a number of internuclear distances on both sides of the equilibrium position. Near Hartree–Fock accuracy is obtained in the SCF calculations. All eight molecules have a range of internuclear distance in which electric dipole moments are of the polarity of A−B+. The shapes of computed electric dipole moment functions are discussed in the language of the molecular orbital method and in relationship to electronegativities of atoms. The present study gives us deeper understanding of electron transfer inside molecules and consequently of the apparent contradiction between electronegativity and the dipole polarity of some molecules. © John Wiley & Sons, Inc.
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

A 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

Explicitly 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

In 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

Rigid 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

Quantum 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

The 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

Starting 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

We 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

By 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

Molecular 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

Traditional 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

Principal 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

A 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

A 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

The 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

The 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.
Combined molecular mechanical and quantum mechanical potential study of a nucleophilic addition reaction in solution
Authors: Liu Haiyan , Shi Yunyu
Published: January 2005

The procedure of combined semiempirical quantum mechanical (AM1) and molecular mechanical potential7 was used to study the nucleophilic addition of hydroxide to formaldehyde in solution. The gas phase AM1 potential surface is approximately 26 kcal/mol more exothermic than the corresponding ab initio 6‐31 + G* calculation results. The free energy profile for the reaction in solution was determined by means of molecular dynamic simulations. The resulting free energy of activation is approximately 5 kcal/mol. The difference of the free energy of solvation between the reactant and the product states is about 38 kcal/mol. As the reaction goes on, the number of hydrogen bonds formed by the hydroxide oxygen with the surrounding water molecules decreases, whereas the number of hydrogen bonds formed by the carbonyl oxygen increases. There is no significant change in the total number of hydrogen bonds between the solute and the solvent molecules, and the average number of these hydrogen bonds is between five and six during the entire reaction process. These results are consistent with previous studies using a model based on ad initio 6‐31 + G* calculations in the gas phase. The reaction path in solution is different from the gas phase minimum energy reaction path. When the two reactants are at a large distance, the attack route of the hydroxide anion in solution is close to perpendicular to the formaldehyde plane, whereas in the gas phase the route is collinear with the carbonyl group. These results suggests that although AM1 does not yield accurate energies in the gas phase, valuable insights into the solvent effects can be obtained through computer simulations with this combined potential. This combined procedure could be applied to chemical reactions within macromolecules, in which a quantitative estimation of the effects of the environment would not be easily attainable by another technique. © 1994 by John Wiley & Sons, Inc.