Eugene M. Fluder

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Similarity searches based on chemical descriptors have proven extremely useful in aiding large-scale drug screening. Typically an investigator starts with a "probe", a drug-like molecule with an interesting biological activity, and searches a database to find similar compounds. In some projects, however, the only known actives are peptides, and the(More)
Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent(More)
Similarity searches using topological descriptors have proved extremely useful in aiding large-scale screening. We describe alternative forms of the atom pair (Carhart et al. J. Chem. Inf. Comput. Sci. 1985, 25, 64-73.) and topological torsion (Nilakantan et al. J. Chem. Inf. Comput. Sci. 1987, 27, 82-85.) descriptors that use physiochemical atom types.(More)
A novel method for computing chemical similarity from chemical substructure descriptors is described. This new method, called LaSSI, uses the singular value decomposition (SVD) of a chemical descriptor-molecule matrix to create a low-dimensional representation of the original descriptor space. Ranking molecules by similarity to a probe molecule in the(More)
We present an application of a novel methodology called Text Influenced Molecular Indexing (TIMI) to mine the information in the scientific literature. TIMI is an extension of two existing methodologies: (1) Latent Semantic Structure Indexing (LaSSI), a method for calculating chemical similarity using two-dimensional topological descriptors, and (2) Latent(More)
Similarity searches based on chemical descriptors have proven extremely useful in aiding large-scale drug screening. Here we present results of similarity searching using Latent Semantic Structure Indexing (LaSSI). LaSSI uses a singular value decomposition on chemical descriptors to project molecules into a k-dimensional descriptor space, where k is the(More)
The similarity and diversity sampling problems are two challenging optimization tasks that arise in the analysis of chemical databases. As a first step to their solution, we propose an efficient projection/ refinement protocol based on the principal component analysis (PCA) and the truncated-Newton minimization method implemented by our package TNPACK(More)
In this study we use a novel similarity search technique called latent semantic structure indexing (LaSSI) with joint chemical probes as queries to mine the MDL drug data report database. LaSSI is based on latent semantic indexing developed for searching textual databases. We use atom pair and topological torsion descriptors in our calculations. The results(More)
A method for grouping Streptomyces strains by fingerprints of their rRNA operons is described. In polyacrylamide gels, multicopy rRNA operon fragments in Streptomyces genomic MseI fingerprints produced intense bands which are well resolved from the less conspicuous low copy fragments interspersed between them. The high intensity multicopy rRNA bands are(More)
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