Compiling structures to pdf-file (linux)

During my job-searching campaign I was once asked to show all the structures that I have synthesized. Drawing 200+ molecules seemed no fun to me. Even opening all .cdx files generated in 3.5 years, to copy-paste in a single one, was too boring. So I’ve used openbabel for this job.

Once I had all the .cdx in one folder I’ve ran

babel *.cdx allStruc.svg -xe -xl -xC
rsvg-convert -f pdf -o allStruc.pdf allStruc.svg

But the output was weird. All the charged molecules were assigned unrealistic charges over +2000, so all my potassium trifluoroborate and ammonium salts were crap.

Then I turned to molconvert tool from Chemaxon, which is free for academic non-commercial use. To convert all .cdx files to correct smiles I used a simple script:

for i in $(ls -1 .|grep .cdx)
~/marvin/bin/molconvert smiles $i -o tmp.smi
cat tmp.smi >> smiles.smi

Followed by openbabel (I’ve decided to sort the molecules by molecular weight so the complexity will increase more or less steadily down the list):

babel smiles.smi allStruc.svg -xe -xl -xC --sort MW
rsvg-convert -f pdf -o allStruc.pdf allStruc.svg

Still, the conversion wasn’t ideal. Particularly, BF3¯ groups were represented as BF2·F¯. Fortunately, simple replacement of SMILES code ‘B(F)F’ to ‘[B-](F)(F)F’ and removal of extra fluoride (‘[F-].’ in SMILES) solved the problem.

So, here we go, the work of 3.5 years as almost square matrix 15×14:

The final result

ASOs for spinal muscular atrophy

In the new paper scientists from Isis Pharmaceuticals report on the development of the new mouse model for spinal muscular atrophy types I and II. The disease emerges from corrupted splicing of the SMN genes. The problem with previous models was that they were either too severe (with complete knockout of the ‘good’ protein), or too mild. So authors attempted to balance the copy number of the protein and create an ‘intermediate’ mouse line. They achieved that by combining ‘mild’ and ‘severe’ alleles and inserting additional human SMN2 gene into corresponding murine locus. So the resulting mice could live long enough and develop the expected neuromuscular pathology with relatively late onset of sympoms.

What’s more exciting is that when mutant mice were treated with the antisense oligo (ASO) targeting the pre-mRNA of SMN2 gene, the lethality and symptoms were improved. Even more surprising was the finding that delivery of the drug into CNS was not required for the improvement. The question remains if this feature translates into patients. Potentially this can lead to better understanding of the SMA pathology, namely if the disease originates in muscles or in neurons and what are the feedback loops between two cell types.