Friday, 8 February 2019

The nature of ligand efficiency

"First they ignore you, then they laugh at you
then they fight you, then you win"
(Sometimes attributed to Mahatma Gandhi)

It's been a bit of a slog but the 'The nature of ligand efficiency' (NoLE) has just been published in Journal of Cheminformatics. As detailed in the previous post, the manuscript proved too spicy for two of the reviewers assigned by Journal of Medicinal Chemistry who did seem rather keen that the readers of that journal not be exposed to the meaninglessness of the ligand efficiency metric. One of the great things about preprints is that we no longer need to take shit from reviewers and, after spicing up the manuscript a bit more, I uploaded it as my first contribution to ChemRxiv. The exercise did teach me a number of lessons that should serve me well when I get round to writing 'The nature of lipophilic efficiency'...

Proofs for NoLE on my desk at Berwick-on-Sea in Blanchisseuse

I believe that NoLE may be the second scientific publication from the village of Blanchisseuse on the north coast of Trinidad (although I'll be happily be proven wrong on this point) and it follows an article in which I gave the editors of a number of ACS journals some unsolicited advice on assay interference. Sir Solomon Hochoy, who was Governor General of Trinidad and Tobago for ten years after independence, grew up in Blanchisseuse and had a house at the far end of the beach where I swim. I met him on the beach a couple of times before he passed away in 1983 and, after that, I would often chat with Lady Thelma who was an expert in the use of the cast net (she said that it was the only way that her cats would eat and, evidently, they were either very numerous or extremely large). I suspect that she would have been able to teach us a thing or two about high throughput screening although I never summoned the courage to ask her exactly how many cats she had.

Steps leading to the Hochoy house

This part of of Blanchisseuse has a long been associated with picong being given in print and my two articles merely follow an established tradition. The journalist BC Pires is married to one of our next door neighbors and he achieved international notoriety for a 1994 column in which he gently poked fun at the ears of a touring England fast bowler:

"He's a bowler with bat ears. How can he bowl fast with ears like that? The wind resistance must be a bitch to overcome, which probably accounts for the odd look of his first four steps. If he had his ears tucked, he'd outpace Ambrose. A less determined man would have opted to bowl spin. I'm amazed that he can walk head-on into the wind, far less run in at a seamer's speed. If, just as he reached the end of his run-up, he tripped at the bowling crease, he would probably glide to the other wicket. He could stump the batsman himself off his own delivery. He could deliver his delivery. He's a gentleman though; he's the only bowler I know who walks with his own sight screen attached to his head."

Needless to say BC was forced to make a grovelling apology and, if forced to make a grovelling apology for any of my scientific articles, I shall certainly consult my old schoolmate who is a (the?) world-leading expert and thought leader in the making of grovelling apologies.

"But Mr Caddick has demanded an apology and so I feel that I must, with utmost sincerity, say that I am very sorry indeed that Andy Caddick has big ears."

"Talk to me, Basil, I'm all ears" (with BC in Barbados)

Like both BC and I, my late father was taught by the Holy Ghost Fathers and the title of his final book was inspired by a rather bizarre episode that had taken place a couple of years before BC was accosted in the commentary box at Bourda by a fast bowler who is 20 cm taller than me (take another look at the photo above as you try to imagine that scene). For decades, a weather vane in the form of a sea serpent had sat harmlessly on the roof of the Red House which is currently being renovated but at the time, housed Parliament. Some years previously, the calypsonian Sugar Aloes had sung that the sea serpent (commonly believed to be a dragon) was a evil omen and, when the People's National Movement (PNM) were re-elected, it was decided that the dragon simply had to go.

The dragon was duly replaced with a white dove in a nocturnal operation that was personally supervised by the Minister for Works. The reason given for installing the dove at night was that they wanted to minimize disruption of traffic and this must be the only occasion on which a government in Trinidad and Tobago has been concerned about disrupting traffic. Although some considered the dove (with an olive branch in its beak) to be masterpiece, others were unconvinced. In particular, there was something that just didn't look right. It was my late father, Professor of Zoology at the University of the West Indies, who identified the problem in a letter to the Daily Express.

"Examination of your photograph shows an aerofoil of mixed parentage. The inner segment resembles that of any small bird with a generalised wing such as a dove a keskidee. The outer segment with its greater width is clearly that of a soaring bird such as a corbeau.

In flight a bird's tail feathers would trail and not be partly spread. If however it was landing the tail fan would be widely spread and the long axis of its body inclined sharply upward to the flight path. In flight, no bird would spread its legs in this way but would trail them. The bird in photograph is clearly not flying or landing normally. 

Zoologically the only circumstances under which this configuration of spread legs, partially spread tail fan and spread primaries is possible is when a bird defecates in flight."            

Masters of picong

No thought leaders, key opinions, cricketers or avifauna were harmed during the production of this blog post.