Use of Mathematical Structural Invariants in Analyzing Combinatorial Libraries: A Case Study with Psoralen Derivatives
Subhash C. Basak,
Brian D. Gute,
Alexandru T. Balaban,
Gregory D. Grunwald.
In this paper, calculated topological indices have been used to cluster a large virtual library of 125 psoralen derivatives into 25 clusters in an effort to select a subset of mutually dissimilar structures from a large collection of molecules. Inspection of the 25 structures, namely the one closest to the respective centroid of each cluster, shows that the molecules are structurally more diverse as compared to a subset of 25 selected randomly. It is expected that such methods based on easily calculated descriptors may find applications in new drug discovery from the analysis of libraries of interesting lead compounds.
Keywords: Chemical clustering, combinatorial library, computational drug design, molecular dissimilarity, molecular similarity, principal component analysis, psoralen, topological index, mathematical formalism, drug discovery, predictive toxicology, Constitutional formulae, connectedness of atoms, chemical bonds, finite non-empty set, structural model, irreflexive symmetric binary relation, symbolize atomic cores, valence electrons, covalent chemical species, transition states, SN2 reactions, pi bonds, molecular branching, enumeration, constitutional isomers, structurephysicochemical property, structure-biology activity, virtual library, binary relation, vertices, linear graph, eccentricity, isomorphic, one mapping, Automorphism, isomorphism, The hydrogen-filled, hydrogen-suppressed graph,, Basak, graph-theoretic, chromatic-number, automorphism group, topologically equivalent, Rashevsky's, non-negative real number, molecular complexity, information-theoretic, information index, POLLY, topostructural, topochemical indices, In silico testing, computational methods, quantitative structure-activity relationship, toxicities, toxic modes of action, combinatorial chemistry, novel lead compounds, potential therapeutic activity, high throughput screening (HTS), screening, innovative leads, distinct clusters, Psoralea coryfolia, treating leukoderma, Ayurvedic medicine, furocoumarins, furanic ring, T-cell lymphoma erythroderma, graft-verus-host disease, photoinactivation, transfusions, immunomodulation, triple helix formation for gene targeting, homogeneity of structure, distance threshold, distance range, pharmaceutical drug design
Rights & PermissionsPrintExport