Conformational Analysis Of Molecules Research Articles

Broadband homonuclear decoupled HSQMBC methods.

Long-range heteronuclear coupling constants convey invaluable information for stereochemical and conformational analysis of molecules from synthetic and natural origin. Here, we report a real-time Zangger-Sterk CPMG-HSQMBC method for the precise and direct measurement of multiple-bond heteronuclear couplings. It is demonstrated that the real-time acquisition strategy combined with multiple slice selective excitation can provide substantial improvement in sensitivity (or reduction of experimental time) as compared to other variants of broadband homonuclear decoupled HSQMBC methods published previously. Scope and limitations of the different strategies applied for decoupling are reviewed. Moreover, practical guidelines for the choice of the most appropriate method are also presented. Applications are given on a metal complex incorporating P-heterocycles and two diglycosyl-selenides for the extraction of n J(1 H, 31 P) and n J(1 H, 77 Se), respectively.

Towards breaking the curse of dimensionality in computational methods for the conformational analysis of molecules

Background In computational molecular biology, the conformational analysis of a molecule refers to the identification of conformations - the clusters of molecular configurations sharing a large-scale geometric structure - and the description of conformation dynamics. These data help to describe the structures and functions of molecules which are relevant in biology. In applications such as computational drug design, they help to identify suitable compounds for disrupting processes involved in disease mechanisms. Today, many computational methods for conformational analysis are mesh-based: they involve discretizing configuration space using regular lattices, and simulating trajectories on energy landscapes. These methods suffer from the ‘curse of dimensionality’ in that the cost increases exponentially with the number of atoms in the molecule. Given that many important molecules in biology - such as proteins have thousands of atoms, the curse of dimensionality severely limits the applicability of these methods. Finding an alternative approach to conformational analysis that does not suffer from the curse of dimensionality would enlarge the set of molecules and biological processes which may be studied using computational methods. Results We construct a mesh-free method [1] using random sampling of energy landscapes, Monte Carlo quadrature, and coarse-graining [2]. We provide proof of concept by testing the method on a toy model of a molecule from the literature and find that the results of our method are comparable to those obtained by an exact, mesh-based method. Using results from linear programming theory and discrete geometry, we establish that the computational cost of our method increases only polynomially with the size of the molecule – an improvement over the exponential increase in the case of mesh-based methods. Conclusions Our findings demonstrate that one does not need meshes for conformational analysis. For the specific problem we study in our paper – that of finding conformations and computing conformation transition rates – our findings suggest that mesh-free methods may be just as accurate as mesh-based methods, while costing less computationally. Our findings emphasize the utility of using ideas from different mathematical fields when devising new methods to tackle computational challenges.

1H-Detected IPAP DEPT-INADEQUATE and IPAP RINEPT-INADEQUATE for the measurement of long-range carbon–carbon coupling constants

The sensitivity of cryoprobes, which are rapidly becoming available, have brought about the possibility of measurement of 13C, 13C coupling constants at the natural abundance of 13C using tens rather than hundreds of milligrams of compounds. This relatively recent development lays the foundation for a more routine use of the 13C, 13C long-range coupling constants in the conformational analysis of molecules. We have designed novel 1H-detected INADEQUATE experiments optimized for long-range 13C, 13C correlations and the measurement of long-range coupling constants. These experiments incorporate refocusing of 1 J CH coupling constants prior to the formation of DQ coherences and 1H-decoupling during the long carbon–carbon evolution intervals. Such modifications significantly enhance their performance over 1H-detected INADEQUATE experiments currently in use for mapping the one-bond 13C, 13C correlations. 1H or 13C polarization is used a starting point in long-range correlation 1H-detected IPAP DEPT-INADEQUATE or RINEPT-INADEQUATE experiments. These correlation experiments were modified yielding in-phase (IP) or antiphase (AP) 13C, 13C doublets in F 1. Procedures were developed for their editing yielding accurate values of small 13C, 13C coupling constants. The methods are illustrated using mono- and disaccharide samples and compared with related 13C-detected experiments by means of the measurement of interglycosidic 13C, 13C coupling constants of a disaccharide.

Molecular mechanics (MM3(π)) conformational analysis of molecules containing conjugated π‐electron fragments: Leucomycin‐V

The conformations of the 16-membered macrolide antibiotic leucomycin-V (1) were studied with molecular mechanics. Leucomycin-V contains a conjugated pi-electron fragment and necessitates special treatment with the MM3(pi) modeling protocol. Comparison was made with results from the standard MM3 scheme. The CONFLEX conformational search procedure was used for finding low-energy conformations. The computed data are indicative for the existence of mainly one conformation of the macro-ring of 1 and minor participation of several others. Intramolecular hydrogen bonds play important roles for the preferred geometry of the macro-ring and the conformations of the side chains. The most probable macro-ring conformation of 1 is very similar to the preferred conformation of another 16-ring macrolide antibiotic, tylosin. The same order of conformational preference for 1 was estimated with the MM3 and the MM3(pi) methods. Surprisingly, when changing the chirality of the C(9) macro-ring atom of 1, the two methods produced different order of conformational preferences for the 9-epi form (2), as well as enhanced population of several clusters of conformations.

Improved Karplus Equations for 3JC1,H4 in Aldopentofuranosides: Application to the Conformational Preferences of the Methyl Aldopentofuranosides

The effects of electronegativity and stereochemistry upon three bond 1H−1H coupling constants (3JH,H) are widely appreciated and have been taken into consideration in the development of Karplus equations for H−C−C−H fragments. These equations have found particular use in the conformational analysis of molecules containing aldopentofuranose residues. This paper demonstrates the effect of anomeric stereochemistry upon 3JC1,H4 in aldopentofuranosides and proposes Karplus equations that account for this effect. These new equations are shown to provide improved results for the determination of furanose ring conformation when compared to those obtained solely with 3JH,H data. The equations described here should be applicable to furanose derivatives containing any substituent at the anomeric center.

Conformational analysis of molecular chains using nano-kinematics.

We present algorithms for 3-D manipulation and conformational analysis of molecular chains, when bond lengths, bond angles and related dihedral angles remain fixed. These algorithms are useful for local deformations of linear molecules, exact ring closure in cyclic molecules and molecular embedding for short chains. Other possible applications include structure prediction, protein folding, conformation energy analysis and 3D molecular matching and docking. The algorithms are applicable to all serial molecular chains and make no assumptions about their geometry. We make use of results on direct and inverse kinematics from robotics and mechanics literature and show the correspondence between kinematics and conformational analysis of molecules. In particular, we pose these problems algebraically and compute all the solutions making use of the structure of these equations and matrix computations. The algorithms have been implemented and perform well in practice. In particular, they take tens of milliseconds on current workstations for local deformations and chain closures on molecular chains consisting of six or fewer rotatable dihedral angles.

Application of vibronic spectroscopy to conformational analysis. Investigations of molecules of carbonyl compounds

Application of vibronic spectroscopy to the conformational analysis of molecules in the ground and excited electronic states is reviewed. The basic concepts of the method as well as its methodological and technical aspects are discussed. The abilities of vibronic spectroscopy are exemplified by the results obtained for molecules of carbonyl compounds.

On the multiple-minima problem in the conformational analysis of molecules: deformation of the potential energy hypersurface by the diffusion equation method

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the multiple-minima problem in the conformational analysis of molecules: deformation of the potential energy hypersurface by the diffusion equation methodLucjan Piela, Jaroslaw Kostrowicki, and Harold A. ScheragaCite this: J. Phys. Chem. 1989, 93, 8, 3339–3346Publication Date (Print):April 1, 1989Publication History Published online1 May 2002Published inissue 1 April 1989https://doi.org/10.1021/j100345a090RIGHTS & PERMISSIONSArticle Views597Altmetric-Citations253LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (864 KB) Get e-Alerts

Optimization of the geometry of the diphenylamine molecule by semiempirical quantum chemical methods

Available data on experimental study of the geometry of the diphenylamine molecule (I) in solution and in the crystal are fragmentary and not always reliable. Previously, they did a conformational analysis of molecule I using the atom-atom potential method. In order to refine the geometric parameters found for molecule I, optimization of its geometry is provided in the paper using the CNDO/2, INDO, MINDO/3 methods with the use of programs for the BESM-6 computer which are part of the VIKING program set. The angles of rotation for the phenyl rings relative to the CNC plane, the bond angles C/sub 2/N/sub 7/C/sub 8/ and C/sub 2/N/sub 7/H/sub 19/, and also the dihedral angle H/sub 19/N/sub 7/C/sub 8/C/sub 9/ were subjected to optimization. For any set of values for the indicated parameters, the bond angle C/sub 8/N/sub 7/H/sub 19/ is determined unambiguously. The results of the calculations are evidence that the MINDO/3 method is not suitable for optimization of the geometry for molecules of the indicated series; in particular, it leads to much too high a value for the CNC angles (135.9/sup 0/). The CNDO/2 method reproduces well the real value of the CNC angle (124.1/sup 0/) and confirms the known pyrimidalmore » character of the nitrogen atom, the sum of the bond angles of which proved to be equal to 353.6/sup 0/. The calculation in the INDO approximation successfully gives the basic characteristics of the molecular geometry of (I); according to this approximation, the CNC angle is equal to 123.2/sup 0/, the CNH angles are equal to 118.0 and 118.8/sup 0/, the sum of the angles for the nitrogen atom is 360.0/sup 0/.« less

The gear effect. VI. Conformational analysis of molecules with two interacting isopropyl groups

The gear effect. VI. Conformational analysis of molecules with two interacting isopropyl groups

Algorithm and program for conformational analysis of molecules by the perturbation-configuration method by use of localized orbitals

Algorithm and program for conformational analysis of molecules by the perturbation-configuration method by use of localized orbitals