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Imagine if given an amino acid sequence, you could quickly calculate what the shape of the corresponding protein would be. You would be able to predict what effect a mutation would have on the shape of the protein. Switching just one glutamic acid with valine completely changes the shape of hemoglobin to the extent that people with this mutation are said to ...


16

Great question! Protein folding has been in open question for decades. Just recently, there's been a lot of discussion regarding DeepMind's AlphaFold project, which was discussed at length on our very own site here. My answer will be complementary to the one above, but the references I will provide will be closer to the physics side of the problem. First ...


15

It's a great question! Some of my answer will be taken from my answer to your question on the AI stack exchange, but cross-site questions are allowed and your question here is slightly different so my answer is slightly different. I'll address your points in reverse chronological order: (4) Most proteins don't have metals at all. It was estimated in 1999 ...


10

Someone more familiar with the problem might have a better suggestion, but I recently came across Daniel B. Dix' notes on Mathematical Models of Protein Folding. This is not my field, so I won't guarantee correctness. However, to a layman at least, these notes seem well suited for someone with your background. The abstract reads We present an elementary ...


7

Preamble Since I don't know your specific background, this is a generic answer for any applied mathematician wishing to enter the field of protein folding. Not everything will apply specifically to you, and please don't feel offended if there's something I assume you don't already know or do! First of all, as a fellow mathematician (I was trained in ...


6

I have found the solution to the problem. One needs to use the animate command to change the frame in the top molecule in VMD. The corrected script which produces the desired output is as follows: set outfile [open ./percent_helix.dat w] set lookup {H G I} set frame_num [molinfo top get numframes] set full [atomselect top "name CA"] set len [...


6

Keep in mind that many if not most proteins have multiple quasi-stable conformations, so their 3D structure is not actually a single conformation but rather a Markov matrix of conformations, with probabilities of a given conformation and probabilities of transition from each conformation to its neighbors varying according to temperature, pH, and other ...


5

Probably one of the important applications is Computer Aided Drug Discovery (CADD). If the protein structure could be accurately predicted, one could design protein-ligand docking on the binding pockets and run molecule dynamics simulations. In the lead identification process of a CADD, the starting point is normally be the experimental data for the crystal ...


5

Here's what I did. Assuming that you have a part of the protein crystal structure. In my case, I have an incomplete structure of the protein. Lets say if I have an amino acid (AA) sequence of 520 (full length), I have the pdb for certain domains which are functionally important. So, I went for homology modelling. I used two predictors Robetta and tr-Rosetta. ...


5

In the past I had the same question and after a long search I found that every two year there is a worldwide competition to assess the quality of 3D structure prediction of proteins. In the past the winner was an online services called I-tasser that you can find here. I tested it also in the past year with the covid spike protein and after the publication of ...


4

I'm adding another answer because I recently find these news. The machine learning-based methods alphafold and rosettafold were recently released on github. Someone has just implemented it in Google colab as Jupiter notebook that you can simply reuse with your colab account. The only thing that you need to do is change the AA sequence. It seems that in the ...


4

Your protocol is right and rigorous in the sense as if you don't have the crystal structure of your protein and want to do some predictions, them the only way is using homology modeling. I am not a big fan of homology modeling, so I always recommend to avoid it as possible. My addition will be that, instead using only one resource to model the 3D structure, ...


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