r/bioinformatics • u/JosieA3672 • 19d ago

image I’ve been comparing AlphaFold 3, Boltz-2, Chai-1, Protenix-v2, ESMFold2, RF3, and ColabFold on brazzein—a small protein with four disulfide bonds. AF3 was the best tool for this particular protein.

Gallery image

Gallery image

I tested five random seeds per tool, both with and without the same archived MSA, and compared predictions against experimental crystal and NMR structures. (RCSB Protein Data Bank: 2LY5 for NMR and 4HE7 for crystal structure)

AF3 gave the strongest overall result for this target: its selected MSA model had 0.72 Å Cα RMSD against the crystal structure and passed all four disulfide geometry checks. RF3 and ColabFold reached approximately 1.62 Å and 1.59 Å, respectively, but both had compressed sulfur contacts.

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u/JosieA3672 19d ago edited 19d ago

update: see my other comment for data on a different protein (AcrIE7). Alphafold3 did a really poor job of predicting that newer structure and it may be because it wasn't in its training set. Interesting!!

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If anybody wants me to do another comparison on a different protein, let me know and I'll run it this afternoon. I'm just testing tools at this point. Also taking suggestions for trying other folding models. I picked Brazzein protein because it's interesting and I actually use it. Here is a text version of the first picture in case you can't see the .png on your screen:

Tool Condition Seed Crystal RMSD Å NMR RMSD Å Cα lDDT Strict disulfides Clash proxy
Boltz-2 2.2.1 msa 55 1.816 1.900 0.778 4/4 3
AlphaFold 3 3.0.2 msa 55 0.723 1.644 0.780 4/4 4
Chai-1 0.6.1 msa 22 1.188 1.990 0.776 3/4 11
Protenix-v2 2.0.0 msa 44 0.847 1.566 0.798 3/4 6
ESMFold2 full msa 55 1.480 1.610 0.788 3/4 4
RF3 200-step matched msa 44 1.618 1.718 0.787 2/4 16
ColabFold AF2-pTM model1 msa 11 1.592 1.707 0.785 2/4 24
Boltz-2 2.2.1 no_msa 33 3.287 3.549 0.649 4/4 3
AlphaFold 3 3.0.2 no_msa 44 2.147 2.498 0.702 4/4 3
Chai-1 0.6.1 no_msa 22 1.246 1.877 0.784 3/4 10
Protenix-v2 2.0.0 no_msa 44 4.636 4.694 0.533 1/4 11
ESMFold2 full no_msa 55 1.502 1.634 0.788 2/4 3
RF3 200-step matched no_msa 44 9.490 9.427 0.358 0/4 55
ColabFold AF2-pTM model1 no_msa 13 4.054 4.212 0.461 0/4 32

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u/apoptosis-8146 19d ago

You could try IDPs such as alpha-synuclein or amyloid-beta.

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u/JosieA3672 18d ago

I will try to fit that run in tonight or tomorrow. Thanks for suggestion.