Shape-similarity analysis of 20 stable conformations of neutral β-alanine

Abstract

Abstract:The family of 20 stable conformations of neutral p-alanine are analyzed in terms of their shape similarities using the topological Shape Group Method, a general molecular shape analysis technique as applied to the three-dimensional electronic density. Molecular electron densities are calculated using the 6-3 IG*" basis set, followed by the determination of the shape groups of local curvature patterns for the entire chemically relevant range of electron density contour surfaces. The results of the shape group analysis are represented by two-dimensional shape maps. Discretized grids of these maps generate numerical shape codes, and comparisons of these numerical codes serve as measures of shape similarity of the various conformers of 0-alanine. This technique is based on direct comparisons of the intrinsic shape features of molecules and requires no superposition of molecules for comparisons. Mathematically well-defined and unbiased similarity measures are obtained by this non-visual, computer-based method, useful for the detection, quantification, and analysis of electronic charge distribution similarities. The family of 20 stable conformers of p-alanine serves as a test case for the application of the methodology for a large number of conformers, representing a level of complexity analogous to that of typical conformational problems in computer-aided drug design and the screening of potential drug molecules for shape similarity.Key words: similarity measures, shape groups, p-alanine, conformation analysis, molecular shape, electron density.RCsumC : On a analysk la famille de 20 conformations stables de la p-alanine neutre en fonction des similitudes de leur forme, en utilisant la Mkthode de groupe de forme topologique. On a appliquk la technique d'analyse de la forme moltculaire gknerale h la densitk klectronique en trois dimensions. On a calcult les densitts moltculaires klectroniques en utilisant l'ensemble de base 6-3 IG**, suivi d'une dktermination des groupes de forme du modele de courbure locale pour tout le domaine chimiquement caractkristique des surfaces de contour de la densit6 Clectronique. On reprksente les rksultats de l'analyse des groupes de forme par des diagrammes de forme en deux dimensions. Des grilles discontinues de ces diagrammes gknbrent des codes de forme numkrique et les comparaisons de ces codes numtriques servent de mesure de la similitude de forme des divers conformeres de la 0-alanine. Cette technique est baske sur la comparaison directe des caractkristiques de formes intrinsbques des moltcules et ne requiert pas, pour les comparaisons, la superposition des molecules. On a obtenu des mesures de similitude bien dtfinies mathkmatiquement et sans influence par cette methode non visuelle baske sur ordinateur, utile pour la dktection, la quantification et l'analyse des similitudes de distribution de la charge tlectronique. La famille des 20 conformbres stables de la 0-alanine sert de cas type pour I'application de la mtthodologie h un plus grand nombre de conformbres, reprksentan...

Basic conformers in ?-peptides

“…This was also found for ␤-alanine itself at various levels of ab initio MO theory. [43][44][45][46] In a recent nmr study on this compound comparable amounts of gauche and anti conformations were estimated. 46 Side chains in the 2-and 3-position of the ␤-amino acid restrict the flexibility of the peptide backbone and cause differences in the conformer patterns of A and B, although most conformers appear in both series (Tables II and III).…”

“…[35][36][37][38][39][40][41][42] It is the aim of this paper to extend these studies to the conformation of ␤-peptides. Until now only few quantum chemical studies on ␤-alanine [43][44][45][46] and N-acetyl-NЈ-methyl-␣-methyl-␤-aspartamide 13 are available. *…”

Computer Aided Drug Design: Some Fundamental Aspects

“…Here we shall provide only a brief summary of these results and some of the literature references involving applications of various relevant topological shape analysis methods [17,18,20,49,[51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. Shape analysis studies of some macromolecules, including proteins, were the very first to derive high accuracy, quantum chemistry quality electron densities for proteins and for drug molecules such a taxol [17,18,20,55], and for the construction of efficient lipophilicity potentials [49,62].…”

“…Similarity approaches and an adaptation of the holographic electron density analysis provided excellent correlations between computed molecular features and experimentally measured optical activities in some chiral compounds [66]. The shape group methods have been applied successfully in a predictive sense to derive toxicity relations in a series of studies [61,[63][64], and to analyze some prototype molecules in drug design applications [58][59][60].…”

FTIR spectra and conformational structure of deutero-β-alanine isolated in argon matrices

“…Ramek located 20 b-alanine conformers using the HF/4-31G level of theory and introduced a nomenclature for identifying the conformers [13] which has been since used in most papers on b-alanine including this work. During the following years numerous computational studies [13][14][15][16][17][18][19] were performed at increasingly higher levels of theory and they provided increasingly more accurate relative stabilities of the b-alanine conformers. A brief review of the studies may be found in Ref.…”