August 2015 newsletter

Applying the XED molecular mechanics force field to the binding mechanism of GPCRs This is the third and final blog in this series ‘Agonist and antagonist differences emerge for the Beta2 Adrenergic GPCR‘ by Andy Vinter. Part 3 reports on the tentative finding that agonists stabilize the full complex and fight to keep the Arg131/Glu

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Electrostatics of the Topliss tree

Since its publication on J. Med. Chem in 1972, J.G. Topliss’ operational scheme for aromatic substitution,1 commonly known as ‘the Topliss tree’, has been widely used by medicinal chemists to explore the substitution pattern on a benzene ring. This decision tree approach was designed for maximum simplicity of application by the medicinal chemists, avoiding use

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Is this compound worth making?

Background In deciding if a compound is worth making medicinal chemists need to consider a number of factors including: does it fit with the known structure activity relationship (SAR)? does it explore new interactions or regions of space? does it have good physico-chemical properties? Summarizing the SAR content of large compound series in a single

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Rapid technique for new scaffold generation II: What is the best source of inspiration?

Background Scaffold hopping and R-group replacement remain central tasks in medicinal chemistry for generating and protecting intellectual property. Spark is a bioisostere replacement tool (available as a desktop software application) for rapidly generating reasonable yet novel scaffold and R-group replacements using Cresset’s molecular field points. Cresset’s field technology condenses the molecular fields down to a

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Examining the diversity of large collections of building blocks in 3D

Abstract 2D fingerprint-based Tanimoto distances are widely used for clustering due the overall good balance between speed and effectiveness. However, there are significant limitations in the ability of a 2D fingerprint-based method to capture the biological similarity between molecules, especially when conformationally flexible structures are involved. Structures which appear to largely differ in functional group

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