Controlling the behavior of compounds and materials by manipulation of molecular properties.
Pat Walters responded to my post on the OpenADMET initiative and I am responding to his post. As is normal for posts here my responses are italicised in red and enclosed in square brackets. Many thanks, Pat, for taking the time to respond to my comments. ******************************** A recent post on the Molecular Design blog by Peter Kenny critiques the OpenADMET initiative. While constructive…
“Quantity has a quality all of its own” Original source unknown The quote with which I’ve opened the post on the OpenADMET initiative is often attributed to Joseph Stalin and some suggest that he might have been referring to the T-34. While the safety and comfort of crews were not priorities for Soviet tank designers the T-34 was a better tank than the quote might be taken to imply. In particular,…
I’ll open the post on the OpenBind initiative with photos from my visit last year to Korea which was timed to coincide with the cherry blossoms (this meant that the customary April Fools post was from Seoul). Things did not start well on the day that I took these photos (having lined up the first shot for the day it became abundantly clear that the camera’s battery was still being charged at the…
I'll open the post with photos that I took in Seoul last year at the Dongdaemun Design Plaza ( DDP ) which was designed by Zaha Hadid (1950-2016) and I'm ashamed to admit to only having become aware of her ten years ago while wandering around the American University of Beirut (she studied mathematics at AUB and much later designed the building there that houses the Issam Fares Institute for Public…
In this blog post I’ll be taking a look at C2026 (Grand Challenges for Predictive Modeling in Small Molecule Drug Discovery) which has been published as a ChemXriv preprint. A well-organized collection of grand challenges can indeed help focus scientific research effort on the most important challenges and I consider C2026 to be welcome relief from the view that we can solve all problems with…
I'll open the post on drug design objectives with photos from a most enjoyable and informative visit to the Australian Synchrotron early in 2010 when I was helping with fragment library design at CSIRO. I’ve been meaning for ages to do a post like this and was finally goaded into action when I recently looked at two short videos from interviews with Sir Demis Hassabis, founder of Google DeepMind…
To start the post I'll share a photo that I took in 2012 of incense sticks at the Truc Lam pagoda near Da Lat. Not long after taking this photo I lost a lens cap (although thankfully not the lens) riding a luge through a forest and would later visit a cricket farm (this was particularly welcome because I had developed a taste for fried crickets during a visit to Cambodia in 2005). I’ll be…
<< previous || next >> PAINS ( p an a ssay in terference compound s ) filters have exerted a hold over the drug discovery community ever since the BH2010 study appeared over 15 years ago. Initially I didn’t take much notice of PAINS filters and, in any case, I’d already moved on from analysis of high-throughput screening (HTS) output by that point (I might add ‘thankfully’ because looking at too…
I'm now in Trinidad and I'll share a 180° panorama from Paramin where I walk for exercise. This district in Trinidad's Northern Range is renowned for its agriculture and the most excellent produce is grown in 'gardens' on steep hillsides. My walk would take about two and a quarter hours if I just walked but it usually takes rather longer because I like to take photos and often stop on the ridge to…
It appears that whoever first described Economics as the ‘Dismal Science’ had never encountered a ligand efficiency metric. I’ll be taking a look at the FK2025 study (Covalent ligand efficiency) in this post and the study has already been reviewed by Dan. Something that I’ve observed repeatedly over the years is that authors of ligand efficiency studies exhibit a lack of understanding of units and…
Whoever first referred to Economics as ‘The Dismal Science’ had clearly never read an article on ‘3Dness’ in drug discovery. My own experience reading articles on this topic is a sensation of having my life force slowly sucked out (I even suggested that reviewing the '3Dness' literature might be considered as an appropriate penance when I recently confessed my sins at St Gallen Cathedral) and the…
Here’s a photo from one of my exercise walks in Paramin and you can see the Caribbean Sea in the distance. This is perhaps my favourite view on the walk because it means that I’ve just got to the top of a particularly brutal hill (cars sometimes struggle to get to the top and on one occasion I watched a car fail miserably in four attempts) although you can’t always see the sea as clearly as in…
<< previous || next >> I arrived in Korea on Friday night and am greatly enjoying it here. Photos below show the Jungbu Dried Seafoods Market near where I'm staying and dinner on Sunday (spicy beef noodles). I visited the War Memorial on Sunday and took selfies with the Shenyang J-6 (Chinese version of MiG-19) 'liberated' by Capt. Lee Woong-pyeong when he defected to South Korea on 25th February…
Given that it was International Women's Day yesterday, I'll open the the post (and blogging for 2025) with a photo of a gravestone at St James' Church in Bramley (Hampshire). In the current post I’ll be taking a look at some aspects of aqueous solvation and Richard Wolfenden’s 1983 “Waterlogged Molecules” article ( W1983 ) is still worth reading today (as an aside, Prof Wolfenden will turn ninety…
********************************************************** My pulse will be quickenin' With each drop of strychnine We feed to a pigeon It just takes a smidgin To poison a pigeon in the park Tom Lehrer, Poisoning Pigeons in the Park | video ********************************************************* I’ll be reviewing the H2024 study (Occurrence of “Natural Selection in Successful Small Molecule Drug…
Previous << || >> Next In an earlier post I considered what it might mean to describe drug design as AI-based. In this post I’ll take a general look at using machine learning (ML) to predict biological activity (and other pharmaceutically-relevant properties) for AI-generated chemical structures. Whether or not ML models ultimately prove to be fit for this purpose it is worth pointing out that…
I'll open the post with a panorama from the summit of Shutlingsloe, sometimes referred to as Cheshire's Matterhorn, which at 506 m above sea level, is the third highest point in the county. When in the UK, I usually come here to mark the solstices and there's usually a good crowd here for the occasion (the winter solstice tends to be less well attended). The LR2024 study (Combining IC 50 or K i…
[This post was updated on 10-Aug-2025 to mention my review of CNM2025 (Return to Flatland) which critically examines ( 35 ) (Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success)] This post was updated on 04-Aug-2024 . I thank Tim Ritchie (see RM2009 | RM2014 ) for bringing YG2003 (Prediction of Aqueous Solubility of Organic Compounds by Topological Descriptors)…
I’ll be reviewing Y2022 (The Time and Place for Nature in Drug Discovery) in this post and stating my position on natural products in modern drug discovery is a good place to start. I certainly see value in screening natural products and natural product-like compounds (especially in phenotypic assays) and there is currently a great deal of interest in chemical probes (I’ll point you toward an…
<< previous || next >> Readers of this blog know that, on more than one occasion, I have denounced the ligand efficiency metric as physically meaningless on the grounds that perception of efficiency varies with the concentration value that defines the standard state. As I argue in NoLE this is clearly thermodynamic nonsense (Pauli might even have suggested that it wasn’t even wrong) and the…
A theory has only the alternative of being true or false. A model has a third possibility: it may be true, but irrelevant. With apologies to Manfred Eigen (1927 - 2019) ****************** [This post was updated on 25-Jun-2024] I've just returned to Cheshire from the Caribbean and, to kick off blogging from 2024 I'll share a photo of the orchids at Berwick-on-Sea on the north coast of Trinidad.…
One piece of general advice that I offer to fellow scientists is to not let the fact that an article has been published in Nature (or any other ‘elite’ journal for that matter) cause you to switch off your critical thinking skills while reading it and the BW2014 article (Chemistry: Chemical con artists foil drug discovery) that I’ll be reviewing in this post is an excellent case in point. My main…
I’ll be taking a look at H2023 (Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes) in this post and this article has also been discussed In The Pipeline . I’ll primarily be discussing the quality criteria for covalent probes in this post although I’ll also comment briefly on chemical matter criteria proposed for degrader probes. The post is intended as a…
I’ll be taking a look at B2023 (Fused Tetrahydroquinolines Are Interfering with Your Assay) in this post. The article has already been discussed in posts at Practical Fragments and In The Pipeline . In anticipation of the stock straw man counterarguments to my criticisms of PAINS filters, I must stress that there is absolutely no suggestion that compounds matching PAINS filters are necessarily…
It’s now time to get back to chemical probes and I’ll be taking a look at S2023 (Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research) which has already been reviewed in blog posts from Practical Fragments , In The Pipeline and the Institute of Cancer Research . Readers of this blog are aware that PAINS filters usually crop up in posts on…