- Oral presentation
- Open Access
What compound should I make next? Using Matched Molecular Series for prospective medicinal chemistry
Journal of Cheminformatics volume 6, Article number: O5 (2014)
A Matched Molecular Pair (MMP) is a pair of compounds which differ only by a well-defined structural transformation [1, 2]. Together with large-scale mining of activity or physicochemical data, matched molecular pair analysis (MMPA) has the potential to aid the design of molecules with improved properties by highlighting favourable transformations.
Here we greatly enhance the performance of MMPA for activity prediction by extending to Matched Molecular Series [3, 4]. While matched pair transforms are typically equally likely to increase activity as decrease it, series of length 3 or more exhibit a much greater preference for a particular activity order. One possible reason for this is that longer series correspond to more and more specific protein environments, while matched pair analysis often suffers from being an average effect.
It will be shown that it is possible to predict, with a known degree of accuracy, what R group should increase/decrease the activity of interest, given an observed ordering of activities for a matched series (Figure 1). Predictions are wholly knowledge-based and interpretable.
Wassermann AM, Dimova D, Iyer P, Bajorath J: Advances in Computational Medicinal Chemistry: Matched Molecular Pair Analysis. Drug Dev Res. 2012, 73: 518-527. 10.1002/ddr.21045.
Griffen E, Leach AG, Robb GR, Warner DJ: Matched Molecular Pairs as a Medicinal Chemistry Tool. J Med Chem. 2011, 54: 7739-7750. 10.1021/jm200452d.
Wassermann AM, Bajorath J: A Data Mining Method To Facilitate SAR Transfer. J Chem Inf Model. 2011, 51: 1857-1866. 10.1021/ci200254k.
Mills JEJ, Brown AD, Ryckmans T, Miller DC, Skerratt SE, Barker CM, Bunnage ME: SAR mining and its application to the design of TRPA1 antagonists. Med Chem Commun. 2012, 3: 174-178. 10.1039/c1md00213a.
About this article
Cite this article
O’Boyle, N.M., Sayle, R. & Boström, J. What compound should I make next? Using Matched Molecular Series for prospective medicinal chemistry. J Cheminform 6, O5 (2014). https://doi.org/10.1186/1758-2946-6-S1-O5
- Specific Protein
- Structural Transformation
- Average Effect
- Matched Pair
- Pair Analysis