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- Title
The importance of molecular complexity in the design of screening libraries.
- Authors
Nilar, Shahul; Ma, Ngai; Keller, Thomas
- Abstract
The one-dimensional model of Hann et al. (J Chem Inf Comput Sci 41(3):856-864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell-Boltzmann distribution has been used to calculate the probability of measuring the sensitivity of the interactions as the asymptotic limits of the distribution better describe the behavior of the interactions under experimental conditions. Based on our model, we hypothesized that molecules of lower complexity are preferred for target based screening campaigns, while augmenting such a library with moieties of moderate complexities maybe better suited for phenotypic screens. The validity of the hypothesis has been assessed via the analysis of the hit rate profiles for four ChemBL datasets for enzymatic and phenotypic screens.
- Subjects
MOLECULAR recognition; COMBINATORICS; MAXWELL-Boltzmann function; INTERMOLECULAR interactions; ENZYMATIC analysis; PHENOTYPES; GENETIC testing; GENE libraries
- Publication
Journal of Computer-Aided Molecular Design, 2013, Vol 27, Issue 9, p783
- ISSN
0920-654X
- Publication type
Article
- DOI
10.1007/s10822-013-9683-1