bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the use of conformationally dependent geometry trends from ab initio dipeptide studies to refine potentials for the empirical force field CHARMM
Authors: Momany Frank A. , Klimkowski Valentine J. , Schäfer Lothar 
Published: January 2005

AbstractPrevious 4‐21G ab initio geometry optimizations of various conformations of the model dipeptides (N‐acetyl N'methyl amides) of glycine (GLY) and the alanine (ALA) have been used to help refine the empirical force constants and equilibrium geometry in the CHARMM force field for peptides. Conformationally dependent geometry trends from ab initio calculations and positions of energy minima on the ab initio energy surfaces have been used as guides in the parameter refinement, leading to modifications in the bond stretch, angle bending, and some torsional parameters. Preliminary results obtained with these refined empirical parameters are presented for the protein Crambin. Results for the cyclic (Ala‐Pro‐DPhe)2 are compared with those from other calculations. It seems that the dihedral angle fit achieved by the new parameters is significantly improved compared with results from force fields whose derivation does not include ab initio geometry trends.
Simulations of internal rotation potential energies for substituted ethanes
Authors: Chung‐Phillips Alice , Stevenson Thomas A. 
Published: January 2005

AbstractTwo approaches to the simulation of internal rotation potential energies in substituted ethanes are formulated for general applications. Called the vicinal Fourier coefficient and vicinal pair energy methods, they differ only in form. The latter procedure has the advantage of yielding energy terms that represent pairwise interactions between vicinal substitutents. As numerical examples, the potential energies of ethane and five of its simple methyl and chloro derivatives are employed to simulate the corresponding energies of two higher derivatives of the series. The initial energy data were calculated by the molecular mechanics method (MM2) with geometry optimizations and the ab initio MO procedure (STO‐3G) with standard geometries. Results indicate that simulated energies are reasonably accurate for the flexible‐rotor model (MM2) and extremely accurate for the rigid‐rotor model (STO‐3G). Deviations appear to be systematic and may be rationalized on the basis of molecular structure.
Different approaches to conformational analysis: A comparison of completeness, efficiency, and reliability based on the study of a nine‐membered lactam
Authors: Böhm Hans‐Joachim , Klebe Gerhard , Lorenz Thomas , Mietzner Thomas , Siggel Lorenz 
Published: January 2005

AbstractDifferent methods such as molecular dynamics, systematic, or stochastic search and a special “generic shape” algorithm have been employed in the conformational analysis of a nine‐membered lactam. Furthermore, crystal data were used to generate conformations of the compound under consideration. The various methods are compared in terms of their efficiency and completeness in the search for conformations with an energy content of up to 60 kJ/mol above the global minimum. Additionally, the generated conformations have been optimized by different techniques, molecular mechanics and quantum chemical calculations, to compare the number of existing local minima and their relative energies and geometries.
A boundary element method for molecular electrostatics with electrolyte effects
Authors: Yoon Byung Jun , Lenhoff A. M. 
Published: January 2005

AbstractA boundary element method is developed to compute the electrostatic potential inside and around molecules in an electrolyte solution. A set of boundary integral equations are derived based on the integral formulations of the Poisson equation and the linearized Poisson‐Boltzmann equation. The boundary integral equations are then solved numerically after discretizing the molecular surface into a number of flat triangular elements. The method is applied to a spherical molecule for which analytical solutions are available. Use is made of both constant and linearly varying unknowns over the boundary elements, and the method is tested for various values of parameters such as the dielectric constant of the molecule, ionic strength, and the location of the interior point charge. The use of the boundary integral method incorporating the nonlinear Poisson‐Boltzmann equation is also briefly discussed.
Conserving energy during molecular dynamics simulations of water, proteins, and proteins in water
Authors: Kitchen Douglas B. , Hirata Fumio , Westbrook John D. , Levy Ronald , Kofke David , Yarmush Martin 
Published: January 2005

AbstractMolecular dynamics simulations have been carried out for a series of systems of increasing complexity including: pure water, a model polypeptide (α‐helical decaglycine) in vacuo, a protein (Pancreatic Trypsin Inhibitor, PTI) in vacuo, and a fully solvated protein (PTI in water). The equations of motion were integrated using Andersen's velocity version of the Verlet algorithm with internal contraints (the RATTLE algorithm). The accuracy with which the equations of motion are integrated has been analyzed for several different simulation conditions. The effects of various nonbonded interaction truncation schemes on the conservation of energy have been examined, including the use of atomic cutoffs, and (neutral group) residue cutoffs. The use of a smoothing function to eliminate the discontinuities in the potential at the cutoff leads to a significant improvement in the accuracy of the integration for each of the systems studied. The accuracy with which the equations of motion are integrated using the RATTLE algorithm for pure water and for the solvated protein are found to be comparable when the nonbonded interactions are tapered with a smoothing function at the cutoff.
The nature of the N  H…︁OC hydrogen bond: An intermolecular perturbation theory study of the formamide/formaldehyde complex
Authors: Mitchell John B. O. , Price Sarah L. 
Published: January 2005

AbstractWe have used Hayes‐Stone Intermolecular Perturbation Theory (IMPT) to study the variation with distance and orientation of the various components of the interaction energy of the N  H…︁O = C hydrogen bonded trans‐ formamide/formaldehyde complex, a model system for hydrogen bonding in proteins. The directionality of the total interaction energy is similar to that of the electrostatic component alone. We have analysed our data in terms of two model atom‐atom intermolecular potentials, using an isotropic functional form and an anisotropic one. The anisotropic form gives an excellent representation of the IMPT potential energy surface, considerably better than the isotropic model, and is comprised entirely of theoretically justified, physically meaningful terms.
Exo‐exo and endo‐endo vicinal proton spin‐spin coupling constants in norbornane and norbornene. An IPPP‐CLOPPA analysis
Authors: Cavasotto C. N. , Giribet C. G. , de Azúa M. C. Ruiz , Contreras R. H. 
Published: January 2005

AbstractThe IPPP‐CLOPPA method is used to study the origin of the difference between exo‐exo and endo‐endo vicinal interproton couplings in norbornane and norbornene. The main pathway defining such couplings is found to be determined by the corresponding CH bonds and antibonds. For this reason they can be considered to be transmitted through space. Contributions from excitations involving MOs of bridge 7 and the CH endo and exo bonds and antibonds are found to be negligible in both compounds. Even though bridges 5–6 and 7 are not included in the coupling pathway, they influence the structure of endo and exo CH bonds, and thus cause the nonequivalence of endo‐endo and exo‐exo couplings. Results obtained with the NNBI method are compared to those of IPPP‐CLOPPA.
Geometry optimization in semiempirical SCF‐MO‐CI calculations
Authors: Pötter T. , Klessinger M. 
Published: January 2005

AbstractIt is shown that up to 50% of the computer time needed for geometry optimization on the (semiempirical) CI level by means of gradients calculated as finite differences can be saved by using “corrected noncentral gradients” in combination with a judiciously chosen first estimate of the Hessian in order to assure fast convergence of the procedure.
A simple method for calculating atomic charges in charged molecular systems of biochemical interest
Authors: Mullay John 
Published: January 2005

AbstractA previously developed method for calculating atomic charge in neutral molecules is modified so as to account for charged molecular species. The method is based on the orbital electronegativity (EN) concept and utilizes an EN equalization principal. Since only one linear equation is required per bond in the molecule, the scheme is extremely simple to use and thus is readily applicable to larger molecules of interest to biochemistry. Atom charge results are compared to ab initio calculations as well as experimental data from NMR and X‐ray diffraction studies. It is shown that the method compares very well even with higher level theoretical methods for a variety of charged molecules including alanine and protonated adenine. It is also shown that NMR chemical shift data for charged amino acids are correlated quite well with atomic charges from the present method. In addition charges obtained from X‐ray diffraction data for both ionic alanine and 2′‐deoxycytidine‐5′‐monophosphate are also reproduced very well.
Algorithms for calculating excluded volume and its derivatives as a function of molecular conformation and their use in energy minimization
Authors: Kundrot Craig E. , Ponder Jay W. , Richards Frederic M. 
Published: January 2005

AbstractA numerical method for calculating the volume of a macromolecule and its first and second derivatives as a function of atomic coordinates is presented. For N atoms, the method requires about 0.3 N ln(N) seconds of CPU time on a VAX‐8800 to evaluate the volume and derivatives. As a test case, the method was used to evaluate a pressure‐volume energy term in energy minimizations of the protein lysozyme at 1000 atm (1 atm = 1.013 × 105 Pa). R.m.s. gradients of 10−4 kcal/mol/Å were obtained at convergence. The calculated structures exhibited pressure‐induced changes which were qualitatively similar to the changes observed in the 1000 atm structure determined by X‐ray crystallography.
Molecular mechanics (MM) and MM‐EHMO conformational analysis of the diastereoisomers of 3‐amino‐1,2,3‐triphenyl‐1‐propyl chloride
Authors: Ivanov Petko M. , Momchilova Tatyana G. , Pojarlieff Ivan G. 
Published: January 2005

AbstractThe conformations of simple alkyl substituted 1,2‐diphenylethanes and the diastereoisomers of 3‐amino‐1,2,3‐triphenyl‐1‐propyl chloride were studied by the MM2 force field with the addition of electrostatic corrections to the aromatic force field as proposed recently by Allinger and Lii (dipole‐dipole interactions) and independently by Pettersson and Liljefors (charge‐charge interactions). Computations were also carried out with a modified version of the MM2 program utilizing the MM3 van der Waals potential function and parameters for C (type 2, sp2 hybridized) and H (type 5). The inclusion of dipole moments for the Csp2Csp3 and Csp2H bonds significantly improves the results. A lower value for the V1 parameter for the torsional unit CarCalCalCar had to be used instead of the MM2 value of 2.1 kcal/mol. Computations were carried out also with the hybrid MM‐EHMO procedure. The latter method appears to work correctly also with 1,2,3‐triphenylpropane systems.
Molecular topology. IV. Regressive vertex degrees (new graph invariants) and derived topological indices
Authors: Diudea Mircea V. , Minailiuc Ovidiu , Balaban Alexandru T. 
Published: January 2005

AbstractNew local graph invariants, “regressive vertex degrees” (which are slightly augmented vertex degrees) are introduced on the basis of decreasing contributions of more remote vertexes to the classical vertex degrees. Several such invariants are proposed (BR, ER, SR) where t (either t = 1 or t = 2) is an operator expressing the attenuation with increasing topological distance, according to formula (1) or (2). With the aid of these new local invariants, new topological indices (global graph invariants), Y (namely BY, EY or SY) are introduced and exemplified. Their ability to express the branching and to order alkanes is investigated. An appendix gives some recursive relationships for computing these indices.
The incorporation of hydration forces determined by continuum electrostatics into molecular mechanics simulations
Authors: Zauhar R. J. 
Published: January 2005

AbstractA new technique is presented for incorporating hydration forces into molecular mechanics simulations. The method assumes the classical continuum approximation, where a solvated molecule is represented as a low‐dielectric cavity of arbitrary shape embedded in a continuous region of high dielectric constant. Electrostatic effects are computed by first calculating the distribution of polarization charge (induced by the configuration of solute fixed charges) at the molecular surface. The hydration force at a particular atom is then found as the sum of the coulombic interaction with the induced surface charge, plus a purely mechanical contribution that arises from the pressure of the polarized solvent as it is pulled toward the solute. A procedure is developed to use the computed hydration forces in conjunction with the CHARMM molecular mechanics package to carry out energy minimizations in which the effects of solvation are explicitly included. This new technique also allows a detailed analysis of the relative balance of coulombic, hydration, and steric energies as a function of molecular conformation. The method is applied to the test case of a zwitterionic tripeptide (LYS‐GLY‐GLU), and the computational results suggest that hydration effects can play a significant role in determining a stable conformation for a solvated polar molecule. The future application to larger molecules is discussed.
A comparative study of the simulated‐annealing and Monte Carlo‐with‐minimization approaches to the minimum‐energy structures of polypeptides: [Met]‐enkephalin
Authors: Nayeem Akbar , Vila Jorge , Scheraga Harold A. 
Published: January 2005

AbstractA comparison of two methods for surmounting the multiple‐minima problem, Simulated Annealing (SA) and Monte Carlo with Minimization (MCM), is presented with applications to [Met]‐enkephalin in the absence and in the presence of water. SA explores a continuous space of internal variables, while MCM explores a discrete space consisting of the local energy minima on that space. Starting from random conformations chosen from the whole conformational space in both cases, it is found that, while SA converges to low‐energy structures significantly faster than MCM, the former does not converge to a unique minimum whereas the latter does. Furthermore, the behavior of the RMS deviations with respect to the apparent global minimum (for enkephalin in the absence of water) shows no correlation with the observed overall energy decrease in the case of SA, whereas such a correlation is quite evident with MCM; this implies that, even though the potential energy decreases in the annealing process, the Monte Carlo SA trajectory does not proceed towards the global minimum. Possible reasons for these differences between the two methods are discussed. It is concluded that, while SA presents attractive prospects for possibly improving or refining given structures, it must be considered inferior to MCM, at least in problems where little or no structural information is available for the molecule of interest.
Molecular simulations of DD‐peptidase, a model ß‐lactam‐binding protein: Synergy between X‐ray crystallography and computational chemistry
Authors: Boyd Donald B. , Snoddy John D. , Lin Ho‐Shen 
Published: January 2005

AbstractUsing computer model building, the three‐dimensional structure of an enzyme from Streptomyces R61 that is inhibited by ß‐lactam antibiotics has been constructed starting from incomplete X‐ray crystallographic data for this 37.4 kDa protein. The so‐called DD‐peptidase catalyzes transpeptidation and hydrolysis of peptides terminating in D‐Ala‐D‐Ala and is a model for bacterial transpeptidases and carboxypeptidases essential in the biosynthesis of the peptidoglycan layer of the cell wall. The structure, which was completed with the SYBYL molecular modeling package, has been refined by energy minimization and molecular dynamics using Quanta/CHARMm software. A simulation of 105 ps was run with waters of solvation in the active site. From these computations, the interatomic distances between the active serine and key residues around the active site were determined. Inadequacies at reproducing geometric details of the ß‐lactam ring of a cephalosporin are pointed out which are typical of most commercially available force fields.
A semiempirical theoretical study of the molecular interaction of cocaine with the biological substrate glycine
Authors: Wu C. S. , Neely W. C. , Worley S. D. 
Published: January 2005

AbstractSemiempirical SCFMO computations of the MNDO and AM1 varieties have been employed to model possible interaction processes for cocaine with the biological substrate glycine. It was found for the gas‐phase species that the most likely interactions occurred as nucleophilic attack of the nitrogen lone pair of glycine on the two carbonyl groups of cocaine. These reactions led to intermediates which further decomposed exothermically to amide and alcohol species. The activation enthalpies for the gas‐phase reactions were predicted to be high (39–46 kcal/mol), but it is believed that such processes could possibly occur by reaction pathways with considerably lower activation energies in the liquid state in the presence of mucus containing olfactory binding protein in vertebrate olfactory reception.
Principal component analysis of dipole moment derivative signs of chloroform
Authors: Suto Elisabete , Ferreira M. M. C. , Bruns Roy E. 
Published: January 2005

AbstractThe use of principal components as a basis for a graphical procedure to analyze polar tensor data is proposed. Molecular orbital and experimental polar tensor data for all possible sign combinations of the ∂p/∂Qj of CHCl3 and CDCl3 are represented graphically as principal component scores facilitating sign selection for the ∂p/∂Qj. The graphs are particularly useful in analyzing an apparent conflict in ∂p/∂Qj sign choices based on the isotopic invariance criterion and molecular orbital results for the A1 symmetry species of these molecules. The numerical impacts of individual sign ambiguities for the ∂p/∂Qj on the polar tensor data are measured by the variances associated with the principal components. Assuming the ∂p/∂Qj sign sets with indeterminate signs provide replicated results for the polar tensor elements, their errors are estimated and compared with errors obtained previously by propagating intensity uncertainties through the polar tensor equations.
Free energy calculations on calcium and magnesium complexes: Protein and phospholipid model systems
Authors: Charifson Paul S. , Hiskey Richard G. , Pedersen Lee G. , Kuyper Lee F. 
Published: January 2005

AbstractFree energy calculations have been performed on a variety of calcium (Ca(II)) and magnesium (Mg(II)) complexes as model systems for protein‐metal, phospholipid‐metal, and protein‐metal‐phospholipid interactions. The major goal of this work was to advance our understanding of Ca(II) ion selectivity in the blood coagulation proteins. The limitations of present force field methods as applied to divalent metal ion‐containing systems is discussed. The effects of different water models, varying nonbond cutoff values, and counterions are evaluated. Additionally, the effects of complete charge transformation between predetermined quantum mechanical states is evaluated in which all of the charges of the metal complexes as well as the van der Waals radii of the metals are perturbed. Protein models include formate, malonate, ethylene‐diaminetetraacetate, and 1,1,4,4 ‐butanetetracarboxylic acid. Phospholipid mimics included methylphosphatidylserine, methylphosphatidylcholine, dimethyl phosphate, and trans‐cyclohexane‐1,3‐diphosphate. The present set of calculations tends to overestimate Mg(II) binding in the various test systems for which experimental results exist, an effect which may in part be due to the lack of explicit polarization/charge transfer terms for all molecules, including water, in the force field. However, these calculations support the notion that coagulation protein selectivity towards Ca(II) is likely due to a greater ease of desolvation of Ca(II) over Mg(II).
Basis sets for geometry optimizations of second‐row transition metal inorganic and organometallic complexes
Authors: Sargent Andrew L. , Hall Michael B. 
Published: January 2005

AbstractModest‐sized basis sets for the second‐row transition metal atoms are developed for use in geometry optimization calculations. Our method is patterned after previous work on basis sets for first‐row transition metal atoms. The basis sets are constructed from the minimal basis sets of Huzinaga and are augmented with a set of diffuse p and d functions. The exponents of these diffuse functions are chosen to minimize both the difference between the calculated and experimental equilibrium geometries and the total molecular energies for several second‐row transition metal inorganic and organon etallic complexes. Slightly smaller basis sets, based on the same Huzinaga minimal sets but augmented with a set of diffuse s and p functions rather than diffuse p and d functions, are also presented. The performance of these basis sets is tested on a wide variety of second‐row transition metal inorganic and organometallic complexes and is compared to pseudopotential basis sets incorporating effective core potentials.
A computer automated structure evaluation (CASE) approach to calculation of partition coefficient
Authors: Klopman Gilles , Wang Shaomeng 
Published: January 2005

AbstractA Computer Automated Structure Evaluation (CASE) approach to the calculation of partition coefficient (log P) has been developed. A linear regression equation was obtained linking the log P value of molecules to some of their fragments as identified by a CASE analysis. The relationship was obtained for a database consisting of 935 compounds (r2 = 0.93, s = 0.39, F(39, 895, 0.05) = 316.5). It was found that this approach produced accurate log P estimations even for complex molecules and, in general, gave better results than previously described techniques.
An unbounded systematic search of conformational space
Authors: Goodman Jonathan M. , Still W. Clark 
Published: January 2005

AbstractA new method for searching internal coordinate conformational space systematically via a continuous‐process procedure is described. Unlike previous systematic search methods, the new scheme generates torsionally remote conformers early in the search. It is also unbounded in that the extent of the search need not be specified at the outset. The search begins at low resolution (120° in torsion angle space) and then goes to higher and higher resolution as all points in space at a given resolution have been searched. The search may run without end or be terminated when new conformers cease to be found or when all space at some maximum allowable resolution has been explored. Conformational searches on several medium‐ and large‐ring molecules using the new method are described and the results are compared with those from certain previously described search methods. It is found that the new method is significantly more efficient than previous procedures at finding all low energy conformers of organic molecules.