Representation of molecular configurations by CAST coding method

A configurational CAST (CAnonical representation of STereochemistry) coding method, which represents relative and absolute configuration, is described. The configurational CAST codes are constructed by canonical rotation of the dihedral angles of the input structure before the CAST codes are assigned. Using the configurational CAST, configurational differences can be distinguished independently of conformational differences. Representation of enantiomers is also achieved by a mirror image conversion method. The CAST representation shows the distinctive characteristics of several diastereomers and conformers that were examined. The method clearly represents the differences in configurations. Applications to organic molecules having complex stereochemistry are also demonstrated.     

Algorithm for advanced canonical coding of planar chemical structures that considers stereochemical and symmetric information

We describe a rigorous and fast algorithm for advanced canonical coding of planar chemical structures based on the algorithm of Faulon et al. (J. Chem. Inf. Comput. Sci. 2004, 44, 427-436). Our algorithm works well even for highly symmetric structures; moreover, an advantage of our algorithm includes providing a rigorous canonical numbering of atoms with a consideration of stereochemistry and recognizing symmetric moieties. The planar structural line notation with the canonical numbering is also fit for use with stereochemical line notation. These capabilities are usable for general purposes in chemical structural coding and are particularly essential for detecting equivalent atoms in NMR studies. This algorithm was implemented on a 13C NMR chemical shift prediction system CAST/CNMR. Applications of the algorithm to several organic compounds demonstrate the practical efficiency of the rigorous coding.     

Fast antimicrobial screen test (FAST): improved screen test for detecting antimicrobial residues in meat tissue

The Fast Antimicrobial Screen Test (FAST) is a simple and quick screening test developed to detect antibiotic and sulfonamide residues in food animal carcasses in slaughter establishments. This microbial inhibition test detects antimicrobials that are allowed to be used in food animals. It has the ability to detect these antimicrobials at or above the allowable limit in carcass kidney fluids in 6 h. Laboratory evaluations show that the lower limit of detection (LLD) of FAST and the Calf Antibiotic and Sulfa Test (CAST) for antibiotics tested was the same, but the LLD for sulfonamides of FAST was lower than the LLD of CAST. Compared with the Swab Test on Premises (STOP) developed in 1977, the LLD's of FAST for both antibiotics and sulfonamides were significantly better. Under field conditions, the sensitivity of FAST and CAST to antibiotic and sulfonamide residues in animal kidneys was not significantly different, but the time required by FAST was significantly lower than CAST (6 versus 18 h). Compared with the STOP, the sensitivity and the range of detection by FAST for all antimicrobials were significantly higher and the testing time was lower (18 versus 6 h).     

CAST/CNMR: highly accurate C NMR chemical shift prediction system considering stereochemistry

Accurate, practical prediction of ¹³C NMR chemical shifts has been achieved with a new system, CAST/CNMR, taking account of stereochemistry. The CAST/CNMR system has solved the critical problem of the accurate distinction of differences and similarities in stereochemical structures around a specific carbon, which has not yet been achieved by any other database-oriented system for prediction of ¹³C NMR chemical shifts. CAST/CNMR uses a three-dimensional structural database together with a ¹³C NMR spectral database. Absolute/relative configurational and conformational structural information are described by the CAST (CAnonical-representation of STereochemistry) coding method. This paper provides an overview of the CAST/CNMR system, and describes its application to two natural products as examples.     

Calf antibiotic and sulfonamide test (CAST) for screening antibiotic and sulfonamide residues in calf carcasses

The Calf Antibiotic and Sulfonamide Test (CAST), a microbial inhibition screening test, was developed for detecting antibiotics and sulfonamides in bob veal calf carcasses. The test uses Bacillus megaterium ATCC 9885 as the indicator organism and Mueller Hinton agar as the growth medium. Compared to Swab Test on Premises (STOP), developed in 1970, this screening test has higher sensitivity and the ability to detect a wider range of veterinary antimicrobial residual drugs, particularly sulfonamides, at lower concentrations. Carcasses that are tested with CAST and suspected of containing chemical residue above tolerance level are retained for confirmation. Disposition of these carcasses are determined upon laboratory result. Routine testing of bob veal calves with CAST allowed the Food Safety and Inspection Service to release most calf carcasses within 24 h post-slaughter, thus conserving shipping and handling resources. However, changes in the regulation in 1990 dictate that disposition of carcasses found to contain violative levels of sulfonamide residues should be based on laboratory findings. The analysis of the data for the years 1990-1994 and 1998 indicate that the use of CAST over the years was significant, and had a direct impact on reduction of residue violations in veal carcasses. With the use of CAST, potentially harmful antimicrobial chemicals entering the human food chain through veal meat have been minimized.     

A spherically averaged representation of the atomic one-particle reduced density matrix

Summary A new way of representing the one-particle reduced density matrix (ODM) of closed-shell atoms in a spherically averaged manner is presented, and connections of this representation to the radial density distributionD(R) and the isotropic reciprocal form factorB(s) are shown. In this representation, certain characteristics of the angular nodal structure of the natural orbitals (NOs) are preserved. Examples of hydrogenic orbitals and near-Hartree-Fock wave functions for some closed-shell atoms are given.     

Compton profiles for ejected electrons: Determination of momentum densities

Electron Compton scattering effects usually lead to the determination of momentum densities in atoms and molecules by cross-section measurements on scattered electrons. Similar information is also shown to be directly available from the study of ejected electrons. The proposed treatment results from a simple alteration of the impulse assumptions and appears to give a satisfactory representation of ejected profiles for medium and high energy electron scattering. Preliminary investigations are discussed here for hydrogen and helium atoms.     

About using the approximate fields to calculate the electrostatic potential distribution of membrane channels

By the example of gramicidine channel, a comparative analysis of different approximate representations (heavy atoms, polar protons, near-by atoms) of AMBER force field has been carried out to calculate the electrostatic potential distribution of ionic channels in biological membranes. The results obtained are compared with the potential computed in a full-atom representation. The use of approximate representations is shown to lead to estimated errors of the potential.     

CAST: A new program package for the accurate characterization of large and flexible molecular systems

The presented program package, Conformational Analysis and Search Tool (CAST) allows the accurate treatment of large and flexible (macro) molecular systems. For the determination of thermally accessible minima CAST offers the newly developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with minimization, and molecular dynamics are implemented as well. For the determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic band, and the umbrella sampling approach. Access to free energies is possible through the free energy perturbation approach. Along with a number of standard force fields, a newly developed symmetry‐adapted perturbation theory‐based force field is included. Semiempirical computations are possible through DFTB+ and MOPAC interfaces. For calculations based on density functional theory, a Message Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)‐accelerated TeraChem program is available. The program is available on request. © 2014 Wiley Periodicals, Inc.     

Halogen and Chalcogen Bond Energies Evaluated Using Electron Density Properties

Halogen (X-bond) and chalcogen bond (Ch−bond) energies for 36 complexes have been obtained at the RI-MP2/def2−TZVP level of theory, involving the heavier halogen and chalcogen atoms (Br, I, Se, Te). We have explored the existence of linear relationships between the interaction energies and the local kinetic energy densities at the bond critical points that characterize the σ-hole interactions (both electronic G(r) and potential V(r) energy densities). Interestingly, we have found strong relationships for halogen and chalcogen bonding energies, especially for the V(r) energy density, thus allowing to estimate the interaction energy without computing the separate monomers. This is also useful to estimate the interaction in monomeric systems (intramolecular X/Ch-bonds), as illustrated using several examples. Remarkably, we have also found a good relationship when in the same representation both halogen and chalcogen atoms are included, thus allowing to use the same empirical correlation for both interactions.     

Representation of molecular structure using quantum topology with inductive logic programming in structure–activity relationships

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.     

Evaluating a Degree of Molecular Symmetry and Chirality

A method of evaluating a degree of molecular symmetry is suggested. The symmetry criteria calculated by this technique are useful for predicting phase transition temperatures in mesogen compounds. Methods of evaluating chirality avoiding molecular representation as a set of simplices are proposed. The efficiency of these methods is verified on model structures belonging to different symmetry groups. The new approach may be used to analyze stereochemical relationships between atoms in a molecule.     

Chemische Bindung anschaulich: die Elektronen-Lokalisierungs-Funktion

The Electron Localization Function (ELF) describes chemical bonding through localized pairs of electrons and gives a quantum mechanical basis to the representation of the chemical bond as a line. Computer graphics produce illustrative and intuitive pictures of the shell structure of atoms, ionic, covalent, and coordinative bonds, or multiple bonds and lone pairs of electrons. Resonance formulas, delocalized bonds, and the space occupied by electron pairs can be visualized in the same manner.     

Expansion of linear combinations of slater-type orbitals in eigenfunctions of the three-dimensional isotropic harmonic oscillator

Several classes of functions related to the Gaussian have been used with success as basis sets for the representation of atomic and molecular orbitals. We have compared the representation of a hydrogen 1s orbital by a sum of Gaussian lobe functions with its expansion in eigenfunctions of the three-dimensional isotropic harmonic oscillator. The lobe functions are shown to achieve better expectation values of the energy, with fewer terms. The lobe functions have the further computational advantage of not containing high powers of the radius. It is concluded that the lobe functions are a superior basis set for use in calculations of the electronic structure of atoms and molecules.     

Drug–protein interaction with Vpu from HIV-1: proposing binding sites for amiloride and one of its derivatives

Vpu is an 81-amino-acid auxiliary protein of the genome of HIV-1. It is proposed that one of its roles is to enhance particle release by self-assembling to form water-filled channels enabling the flux of ions at the site of the plasma membrane of the infected cell. Hexamethylene amiloride has been shown to block Vpu channel activity when the protein is reconstituted into lipid bilayers. In a docking approach with monomeric, pentameric and hexameric bundle models of Vpu corresponding to the transmembrane part of the protein, a putative binding site of hexamethylene amiloride is proposed and is compared with the site for the nonpotent amiloride. The binding mode for both ligands is achieved by optimizing hydrogen bond interactions with serines. Binding energies and binding constants are the lowest for protonated hexamethylene amiloride in the pentameric bundle. Figure The proposed binding site of the Vpu channel blocker hexamethylene amiloride within the lumen of the Vpu bundle. The bundle is a homo-pentamer with each monomer consisting of the first 32 amino acids of Vpu including the transmembrane part of the protein which is encoded by HIV-1. The bundle atoms are shown in their van der Waals representation and the helix backbone in a ribbon representation. Residues Trp-23 and Ser-24 are highlighted as sticks. Hexamethylene amiloride is shown in yellow (C atoms) and blue (N atoms)     

Practical modeling of molecular systems with symmetries

A new method for efficient modeling of macromolecular systems with symmetries is presented. The method is based on a hierarchical representation of the molecular system and a novel fast binary tree‐based neighbor list construction algorithm. The method supports all types of molecular symmetry, including crystallographic symmetry. Testing the proposed neighbor list construction algorithm on a number of different macromolecular systems containing up to about 200,000 of atoms shows that (1) the current binary tree‐based neighbor list construction algorithm scales linearly in the number of atoms for the central subunit, and sublinearly for its replicas, (2) the overall computational overhead of the method for a system with symmetry with respect to the same system without symmetry scales linearly with the cutoff value and does not exceed 50% for all but one tested macromolecules at the cutoff distance of 12 Å. (3) the method may help produce optimized molecular structures that are much closer to experimentally determined structures when compared with the optimization without symmetry, (4) the method can be applied to models of macromolecules with still unknown detailed structure. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Bound state methods for elastic scattering phase shifts

Three methods are investigated for obtaining elastic phase shifts in the scattering of electrons from atoms and ions that use a bound-state representation of the scattering wavefunction. Results for singlet p-wave scattering by H and by He⁺ are compared with previous calculations.     

Empirical energy functions for energy minimization and dynamics of nucleic acids

An improved empirical energy function for energy minimization and dynamics calculations of nucleic acids is developed and evaluated by an examination of its representation of both static and dynamic properties of model systems. Among the properties studied and used for parameter optimization are base pairing interactions, sugar and phosphate energy surfaces, small crystal heats of sublimation, base, phosphate and sugar analogue vibration spectra, and the overall behavior of a DNA hexamer duplex in vacuum molecular dynamics simulations. The results obtained are compared with those from two other energy functions that have been used recently for nucleic acids. Parameters for two energy functions are given; one includes heavy atoms and only polar hydrogens and the other includes all atoms.