Published in Journal of Computer-Aided Molecular Design
The conformational profiles of Peptide T, (5–8)Peptide T, [Abu5](4–8)Peptide T and (4–8)Peptide T were computed independently to assess the geometrical characteristics of the bioactive conformation of Peptide T. The conformational profiles of the peptides were computed within the molecular mechanics framework using an effective dielectric constant ...
Published in Journal of Computer-Aided Molecular Design
By means of an error back-propagation artificial neural network, a new method to predict the torsion angles χ, ζ and α from torsion angles δ, ∈, β and γ for nucleic acid dinucleotides is introduced. To build a model, training sets and test sets of 163 and 81 dinucleotides, respectively, with known crystal structures, were assembled. With 7 hidden u...
Published in Journal of Computer-Aided Molecular Design
Lead finding strategies in pharmaceutical research comprise structure-based drug design as well as screening efforts of natural product pools or large chemical libraries. In this context we propose a combined approach by utilizing natural product-derived structure information on receptor- or enzyme-complementarity for designing unique core structur...
Published in Journal of Computer-Aided Molecular Design
Recently, the multilinear PLS algorithm was presented by Bro and later implemented as a regression method in 3D QSAR by Nilsson et al. In the present article a well-known set of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxybenzamides, with affinity towards the dopamine D2 receptor subtype, was utilised for the validation of the multilinear PLS m...
Published in Journal of Computer-Aided Molecular Design
Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active,...
Published in Journal of Computer-Aided Molecular Design
A simple and fast method to calculate charge distributions in organic molecules is presented. The method is based on charge shifts within the saturated σ-system, driven by orbital electronegativities, coupled to a modified Hückel treatment of the unsaturated π-systems. Experimental molecular dipole moments of a set of 119 molecules are reproduced w...
Published in Journal of Computer-Aided Molecular Design
The probable binding mode of the herpes simplex virus thymidine kinase (HSV1 TK) N2-[substituted]-phenylguanine inhibitors is proposed. A computational experiment was designed to check some qualitative binding parameters and to calculate the interaction binding energies of alternative binding modes of N2-phenylguanines. The known binding modes of t...
Published in Journal of Computer-Aided Molecular Design
A recent method for estimating ligand binding affinities is extended. This method employs averages of interaction potential energy terms from molecular dynamics simulations or other thermal conformational sampling techniques. Incorporation of systematic deviations from electrostatic linear response, derived from free energy perturbation studies, in...
Published in Journal of Computer-Aided Molecular Design
Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as we...
Published in Journal of Computer-Aided Molecular Design
Geometry optimizations for several spin states of the iron(III)-S-methyl-porphyrin complex, the iron(III)-oxo-S-methyl-porphyrin complex and the respective anions were performed in order to examine models for intermediates in the oxidative cycle of cytochrome P450. The aim of this study was to obtain insights into the ground states of the intermedi...
