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| 2. |
- Linusson, Anna, et al.
(författare)
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Statistical Molecular Design of Building Blocks for Combinatorial Chemistry
- 2000
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 43:7, s. 1320-8
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Tidskriftsartikel (refereegranskat)abstract
- The reduction of the size of a combinatorial library can be made in two ways, either base the selection on the building blocks (BB's) or base it on the full set of virtually constructed products. In this paper we have investigated the effects of applying statistical designs to BB sets compared to selections based on the final products. The two sets of BB's and the virtually constructed library were described by structural parameters, and the correlation between the two characterizations was investigated. Three different selection approaches were used both for the BB sets and for the products. In the first two the selection algorithms were applied directly to the data sets (D-optimal design and space-filling design), while for the third a cluster analysis preceded the selection (cluster-based design). The selections were compared using visual inspection, the Tanimoto coefficient, the Euclidean distance, the condition number, and the determinant of the resulting data matrix. No difference in efficiency was found between selections made in the BB space and in the product space. However, it is of critical importance to investigate the BB space carefully and to select an appropriate number of BB's to result in an adequate diversity. An example from the pharmaceutical industry is then presented, where selection via BB's was made using a cluster-based design.
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| 3. |
- Linusson, Anna, et al.
(författare)
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Statistical Molecular Design, Parallel Synthesis, and Biological Evaluation of a Library of Thrombin Inhibitors
- 2001
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 44:21, s. 3424-39
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Tidskriftsartikel (refereegranskat)abstract
- A library of thrombin inhibitors has been designed using statistical molecular design. An aromatic scaffold was used, with three varied positions corresponding to three pockets at the active site of thrombin (the S-, P-, and D-pockets). The selection was performed in the building block space, and previously acquired data were included in the design procedure. The design resulted in six, four, and six building blocks for the first (S), second (P), and third (D) pockets, respectively. A second round of selection applied to the combined selected building blocks resulted in a subset of 18 compounds. The selected library was synthesized in parallel and biologically evaluated. The compounds were analyzed with respect to their inhibition (pIC50) of thrombin; membrane permeability, estimated by migration behavior in micellar media (CE log k') and pKa; and specificity with respect to inhibition (Ki) of trypsin. Multivariate QSAR studies of the responses yielded valuable results and information that could only be found using statistical molecular design in combination with multivariate analysis.
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| 4. |
- Pham, Lan Anh
(författare)
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On avoiding and completing edge colorings
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- These papers are all related to the problem of avoiding and completing an edge precoloring of a graph. In more detail, given a graph G and a partial proper edge precoloring φ of G and a list assignment L for every non-colored edge of G, can we extend the precoloring to a proper edge coloring avoiding any list assignment? In the first paper, G is a d-dimensional hypercube graph Qd, a partial proper edge precoloring φ and every list assignment L must satisfy certain sparsity conditions. The second paper still deals with d-dimensional hypercube graph Qd, but the list assignment L for every edge of Qd is an empty set and φ must be a partial proper edge precoloring of at most (d - 1) edges. For the third paper, G can be seen as a complete 3-uniform 3-partite hypergraph, every list assignment L must satisfy certain sparsity conditions but we do not have a partial proper edge precoloring φ on edges of G.
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| 6. |
- Wold, Svante, et al.
(författare)
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The utility of multivariate design in PLS modeling
- 2004
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Ingår i: Journal of Chemometrics. - : Wiley. - 0886-9383 .- 1099-128X. ; 18:3-4, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the use of multivariate design to ensure representativity and balance of the training set data for PLS multivariate modeling. Three application areas are used to illustrate the discussion, namely multivariate calibration in process analytical chemistry, quantitative structure activity relationships (QSAR) in medicinal and pharmaceutical chemistry, and data mining. In both QSAR and data mining, the multivariate design is also useful for the balanced sampling of data from a large, complex, and unbalanced data repository.
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