We describe and demonstrate a method for the simultaneous, fully flexible alignment of multiple molecules with a common biological activity. The key aspect of the algorithm is that the alignment problem is first solved in a lower dimensional space, in this case using the one-dimensional representations of the molecules. The three-dimensional alignment is then guided by constraints derived from the one-dimensional alignment. We demonstrate using 10 hERG channel blockers, with a total of 72 rotatable bonds, that the one-dimensional alignment is able to effectively isolate key conserved pharmacophoric features and that these conserved features can effectively guide the three-dimensional alignment. Further using 10 estrogen receptor agonists and 5 estrogen receptor antagonists with publicly available cocrystal structures we show that the method is able to produce superpositions comparable to those derived from crystal structures. Finally, we demonstrate, using examples from peptidic CXCR3 agonists, that the method is able to generate reasonable binding hypotheses.
This year at TREC 2002 we participated in the adaptive filtering sub-task of the filtering track with some models for training a Rocchio classifier. Results were poorer than average on the utility type measures. Using simple feature selection produced better than average results on an F-type measure. The key to our approach was the use of pseudojudgments, and an approach to threshold updating. We also participated in the batch filtering sub-task of the filtering track and investigated the use of rank based feature selection techniques in conjunction with a very simple classification rule.
This chapter examines core tonal properties of Nata, a Lacustrine Bantu language (Guthrie E-45) spoken in the Mara region of Tanzania. In most instances, both in nouns and verbs, a Nata word exhibits a single high tone, which is restricted to a small number of locations. Though Nata’s tone system might appear simple, close examination of nouns and verbs uncovers considerable complexity in the system. Nouns exhibit lexically encoded distinctions; verb roots exhibit no lexical distinctions, but inflected verbs differ tonally depending on tense/aspect/mood. The sparse distribution of high tones follows from simple edge effects whereby tones are located relative to well-motivated morphosyntactic boundaries. The analysis, framed in a lexical allomorphy approach, crucially depends on correct identification of the macrostem, with a novel aspect being the extension of the macrostem to nouns. This extension is adopted on the grounds that nouns and verbs share similar surface patterns, captured by reference to a common domain.
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