HOME- Bryn Mawr Conference
- Workshops & Training
- 2010 Oxford (Discovery)
- 2010 Oxford (ADMET)
- 2009 Oxford (Discovery)
- Blanchard, H
- Bryant, S
- Coveney, P
- Hardy, B
- Hawkins, P
- Klamt, A
- Knapp, S
- Kranz, M
- Liebeshuetz, J
- Oledzki, P
- Pirok, G
- Wolber, G
- Zamora, I
- Bursary Award
- 2009 Oxford (ADMET)
- 2008 Oxford
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Over the last 8 years, Michael Kranz has supported various stages of the drug discovery process with computational methods at GlaxoSmithKline over a range of different target classes, from classical drug proteins like 7TM’s and enzymes to those involved in epigenetics. He had come to the world of molecular modelling from the nomadic life of a postdoctoral peddler of ab initio truths due to the appearance of 3 DNA replicates in quick succession. At Cambridge University UK, he investigated the transition structures for the peptide bond formation while also supporting a GlaxoWellcome medicinal chemistry team. At Urbana-Champaign, Illinois, in Prof. Denmark’s labs, Michael worked experimentally and computationally on the reactive intermediates of the Wittig reaction. He started his career under the supervision of Professor Schleyer and Tim Clark in Erlangen, Germany, on the theoretical prediction and isolation of dilithiated organic molecules.
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Ligand Structure Calculation, Bioactive Conformations & Conformational Search
Michael Kranz (GlaxoSmithKline)
The vast majority of prescription drugs are small organic molecules. In their quest for new synthetic remedies, chemists need to understand the structural and energetic behaviour of drug-sized molecules. In this workshop, we will look at the properties of small molecules at different levels of theory and compare the results with experimental benchmarks.
The most straightforward way to determine the likely structure of a drug molecule is to perform a conformational search. Hands-on exercises with a number of force fields will lead to a discussion of pros and cons of the most commonly used methods. Their results are contrasted with experiments with particular reference to bioactive conformations.
The field of ab initio calculations has traditionally been shunned by pharmaceutical modellers. The emergence of more powerful hardware together with faster algorithms has brought this technique into the realm of drug discovery. We will establish tautomeric and rotational equilibria during the workshop. The results can be referenced against experiment in the crystallographic databases. Successful applications and new approximations (e.g. fragment MO) that allow the treatment of large proteins will be presented. Molecular properties such as dipole moments and electrostatic fields can be rapidly calculated and visualised. We will determine the H bond acceptor strength for a set of molecules that cannot be derived from single molecule calculations and calculate an IR spectrum.
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