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Multivariate Design and Modelling in QSAR, Combinatorial Chemistry, and Bioinformatics

  • Chapter
Molecular Modeling and Prediction of Bioactivity

Abstract

The last decade has witnessed much progress in how to characterize and describe chemical structure, how to synthesize large sets of compounds, how to make simple and fast in-vitro assays, and how to determine the structure (sequence) of our genetic material. The possible consequences of this progress for drug design are great and exciting, but also bewilderingly complicated.

Fortunately, the last decade has also seen progress in how to investigate and model complicated systems, of which relationships between chemical structure and biological activity provide typical examples. These relationships are central in drug design and some related areas, notably combinatorial chemistry and bioinformatics.

The essential steps in the investigation of complicated systems include the following:

  1. 1.

    The appropriate quantitative parameterization of its parts (here the varying parts of the chemical structures / biopolymer sequences).

  2. 2.

    The appropriate measurements of the interesting properties of the system (here the “biological effects”).

  3. 3.

    Selecting a representative set of molecules (or other systems) to investigate and make the following measurements.

  4. 4.

    The analysis of the resulting data.

  5. 5.

    The interpretation of the results.

The use of multivariate characterization, design, and modelling in these steps will be discussed in relation to drug design, combinatorial chemistry (which compounds to make and test, and how to deal with the biological test results), and bioinformatics (how to parameterize and analyze biopolymer sequences).

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Author information

Authors and Affiliations

  1. Research Group for Chemometrics, Department of Organic Chemistry, Institute of Chemistry, Umeå University, SE-904 87, Umeå, Sweden

    Svante Wold, Michael Sjöström, Per M. Andersson, Anna Linusson, Maria Edman, Maria Sandberg & Lise-Lott Uppgård

  2. Structure Property Optimization Center (SPOC), Pharmacia & Upjohn AB, SE-751 82, Uppsala, Sweden

    Torbjörn Lundstedt

  3. Medicinal Chemistry, Astra Hässle AB, SE-431 83, Mölndal, Sweden

    Bo Nordén

Authors
  1. Svante Wold
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  2. Michael Sjöström
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  3. Per M. Andersson
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  4. Anna Linusson
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  6. Torbjörn Lundstedt
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  7. Bo Nordén
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  8. Maria Sandberg
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  9. Lise-Lott Uppgård
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Editor information

Editors and Affiliations

  1. H. Lundbeck A/S, Valby, Denmark

    Klaus Gundertofte

  2. Royal Danish School of Pharmacy, Copenhagen, Denmark

    Flemming Steen Jørgensen

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Wold, S. et al. (2000). Multivariate Design and Modelling in QSAR, Combinatorial Chemistry, and Bioinformatics. In: Gundertofte, K., Jørgensen, F.S. (eds) Molecular Modeling and Prediction of Bioactivity. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4141-7_2

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  • DOI: https://doi.org/10.1007/978-1-4615-4141-7_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6857-1

  • Online ISBN: 978-1-4615-4141-7

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