Ash Jogalekar
@ashjogalekar.bsky.social
I write about medicinal and computational chemistry and drug discovery with a sprinkling of history. Blog at medchemash.substack.com.
That's usually a good sign that you need to switch to an alternative protocol.
July 23, 2025 at 5:54 PM
That's usually a good sign that you need to switch to an alternative protocol.
In today's version of "How selective might this compound be?"
July 22, 2025 at 10:14 PM
In today's version of "How selective might this compound be?"
I'm glad chatGPT can now use RDKit, but as my query to draw vemurafenib and illustrate its tautomers shows, there's work to be done, especially since that's not vemurafenib and those are not its tautomers.
July 3, 2025 at 11:30 PM
I'm glad chatGPT can now use RDKit, but as my query to draw vemurafenib and illustrate its tautomers shows, there's work to be done, especially since that's not vemurafenib and those are not its tautomers.
One of the underappreciated aspects of a totalitarian state is that everyday life becomes boring as hell (Shirer).
June 10, 2025 at 8:02 PM
One of the underappreciated aspects of a totalitarian state is that everyday life becomes boring as hell (Shirer).
An underappreciated but fascinating book: Chemist John Sheehan's "The Enchanted Ring" which describes his incredible 15 year odyssey to synthesize penicillin. The molecule was devilishly hard to make because it was like a coiled spring; Sheehan found the clamp to hold it together.
May 23, 2025 at 6:36 PM
An underappreciated but fascinating book: Chemist John Sheehan's "The Enchanted Ring" which describes his incredible 15 year odyssey to synthesize penicillin. The molecule was devilishly hard to make because it was like a coiled spring; Sheehan found the clamp to hold it together.
When a tyrant says something that sounds extreme or preposterous, believe him (Shirer).
May 20, 2025 at 9:59 PM
When a tyrant says something that sounds extreme or preposterous, believe him (Shirer).
An example of tacit knowledge in organic synthesis from "Breaking Bad."
May 6, 2025 at 5:27 PM
An example of tacit knowledge in organic synthesis from "Breaking Bad."
Digging through some old stuff I discovered these transparencies - yes, those things - that I made for a science talk in college and now I feel officially old.
April 29, 2025 at 7:12 PM
Digging through some old stuff I discovered these transparencies - yes, those things - that I made for a science talk in college and now I feel officially old.
I’ll get back to you in a week.
April 29, 2025 at 7:10 PM
I’ll get back to you in a week.
You can see Linus Pauling on the far right. Just before attending the reception he had picketed outside the White House, protesting the Kennedy administration’s position on nuclear tests. It says something about both Pauling’s and JFK’s character that Pauling was still part of the reception.
April 29, 2025 at 4:40 PM
You can see Linus Pauling on the far right. Just before attending the reception he had picketed outside the White House, protesting the Kennedy administration’s position on nuclear tests. It says something about both Pauling’s and JFK’s character that Pauling was still part of the reception.
Carl Sagan on the wisdom of the founding fathers.
April 28, 2025 at 9:22 PM
Carl Sagan on the wisdom of the founding fathers.
In a list of august and very worthy contenders, Carl Sagan singles out FLP v1 as “the most consistently exciting, provocative, and inspiring science popularization of the last few decades.”
April 28, 2025 at 9:21 PM
In a list of august and very worthy contenders, Carl Sagan singles out FLP v1 as “the most consistently exciting, provocative, and inspiring science popularization of the last few decades.”
A particularly pleasing application of atropisomer control in the design of Sotorasib, the first approved drug for targeting KRAS. Increasing the barrier by 4 kcal/mol resolved the problem. And variable temperature NMR is great for measuring these energy differences. pubs.acs.org/doi/10.1021/...
April 28, 2025 at 4:54 PM
A particularly pleasing application of atropisomer control in the design of Sotorasib, the first approved drug for targeting KRAS. Increasing the barrier by 4 kcal/mol resolved the problem. And variable temperature NMR is great for measuring these energy differences. pubs.acs.org/doi/10.1021/...
Novel carbodiimide warheads for aspartate covalent targeting. The field marches on. pubs.acs.org/doi/abs/10.1...
April 25, 2025 at 4:25 AM
Novel carbodiimide warheads for aspartate covalent targeting. The field marches on. pubs.acs.org/doi/abs/10.1...
Another example from the GPCR field - there's a lot of these in that one - of a relatively small structural change turning an agonist into an inverse agonist/antagonist. pubs.acs.org/doi/10.1021/...
April 25, 2025 at 4:18 AM
Another example from the GPCR field - there's a lot of these in that one - of a relatively small structural change turning an agonist into an inverse agonist/antagonist. pubs.acs.org/doi/10.1021/...
Classic review from my dear friend and mentor Jeff Seeman.
April 24, 2025 at 5:46 PM
Classic review from my dear friend and mentor Jeff Seeman.
One of the most useful tables for a chemist to remember, and it illustrates why computational chemistry and drug design are hard: even a 1.3 kcal/mol error in calculating an equilibrium conformational or binding free energy difference will essential translate into a 90:10 estimation error
April 24, 2025 at 5:20 PM
One of the most useful tables for a chemist to remember, and it illustrates why computational chemistry and drug design are hard: even a 1.3 kcal/mol error in calculating an equilibrium conformational or binding free energy difference will essential translate into a 90:10 estimation error
April 24, 2025 at 12:05 AM
As someone who has looked at H/D exchange data to gain insight into modeling protein-ligand structures, this paper was of interest to me. D2O is not as benign as you think.
April 22, 2025 at 4:00 PM
As someone who has looked at H/D exchange data to gain insight into modeling protein-ligand structures, this paper was of interest to me. D2O is not as benign as you think.
Neat illustration of the half-lives of cleavage for various bonds in DNA and RNA [in square brackets] at 25 and 92 degrees. Notice the enormous reduction in half-lives brought about by temperature (from Wolfenden, Annu. Rev. Biochem., 2011, 80, 645-67)
April 22, 2025 at 3:42 AM
Neat illustration of the half-lives of cleavage for various bonds in DNA and RNA [in square brackets] at 25 and 92 degrees. Notice the enormous reduction in half-lives brought about by temperature (from Wolfenden, Annu. Rev. Biochem., 2011, 80, 645-67)
In today’s edition of “what could go wrong.”
April 22, 2025 at 12:50 AM
In today’s edition of “what could go wrong.”
“Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order." - Sydney Brenner
April 21, 2025 at 4:51 PM
“Progress in science depends on new techniques, new discoveries, and new ideas, probably in that order." - Sydney Brenner
The fact that these two reactions happen at all, let alone so speedily under mild conditions, is nothing short of astonishing. The power of proximity cannot be exaggerated (Menger, Pure Appl. Chem. 2005).
April 20, 2025 at 5:24 AM
The fact that these two reactions happen at all, let alone so speedily under mild conditions, is nothing short of astonishing. The power of proximity cannot be exaggerated (Menger, Pure Appl. Chem. 2005).