Rapid Quantification of Molecular Diversity for Selective Database Acquisition

There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities

Models for Antitubercular Activity of 5′-O-[(N-Acyl)sulfamoyl]adenosines

The relationship between topological indices and antitubercular activity of 5′-O-[(N-Acyl)sulfamoyl]adenosines has been investigated. A data set consisting of 31 analogues of 5′-O-[(N-Acyl)sulfamoyl]adenosines was selected for the present study. The values of numerous topostructural and topochemical indices for each of 31 differently substituted analogues of the data set were computed using an in-house computer program. Resulting data was analyzed and suitable models were developed through decision tree, random forest and moving average analysis (MAA). The goodness of the models was assessed by calculating overall accuracy of prediction, sensitivity, specificity and Mathews correlation coefficient. Pendentic eccentricity index – a novel highly discriminating, non-correlating pendenticity based topochemical descriptor – was also conceptualized and successfully utilized for the development of a model for antitubercular activity of 5′-O-[(N-Acyl)sulfamoyl]adenosines. The proposed index exhibited not only high sensitivity towards both the presence as well as relative position(s) of pendent/heteroatom(s) but also led to significant reduction in degeneracy. Random forest correctly classified the analogues into active and inactive with an accuracy of 67.74%. A decision tree was also employed for determining the importance of molecular descriptors. The decision tree learned the information from the input data with an accuracy of 100% and correctly predicted the cross-validated (10 fold) data with accuracy up to 77.4%. Statistical significance of proposed models was also investigated using intercorrelation analysis. Accuracy of prediction of proposed MAA models ranged from 90.4 to 91.6%

Information Indices with High Discriminative Power for Graphs

In this paper, we evaluate the uniqueness of several information-theoretic measures for graphs based on so-called information functionals and compare the results with other information indices and non-information-theoretic measures such as the well-known Balaban index. We show that, by employing an information functional based on degree-degree associations, the resulting information index outperforms the Balaban index tremendously. These results have been obtained by using nearly 12 million exhaustively generated, non-isomorphic and unweighted graphs. Also, we obtain deeper insights on these and other topological descriptors when exploring their uniqueness by using exhaustively generated sets of alkane trees representing connected and acyclic graphs in which the degree of a vertex is at most four

Structuprint: a scalable and extensible tool for two-dimensional representation of protein surfaces

© 2016 Kontopoulos et al.Background: The term molecular cartography encompasses a family of computational methods for two-dimensional transformation of protein structures and analysis of their physicochemical properties. The underlying algorithms comprise multiple manual steps, whereas the few existing implementations typically restrict the user to a very limited set of molecular descriptors. Results: We present Structuprint, a free standalone software that fully automates the rendering of protein surface maps, given - at the very least - a directory with a PDB file and an amino acid property. The tool comes with a default database of 328 descriptors, which can be extended or substituted by user-provided ones. The core algorithm comprises the generation of a mould of the protein surface, which is subsequently converted to a sphere and mapped to two dimensions, using the Miller cylindrical projection. Structuprint is partly optimized for multicore computers, making the rendering of animations of entire molecular dynamics simulations feasible. Conclusions: Structuprint is an efficient application, implementing a molecular cartography algorithm for protein surfaces. According to the results of a benchmark, its memory requirements and execution time are reasonable, allowing it to run even on low-end personal computers. We believe that it will be of use - primarily but not exclusively - to structural biologists and computational biochemists