<html><head><meta http-equiv="Content-Type" content="text/html; charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; line-break: after-white-space;" class="">Hi Yunsik,<div class=""><br class=""></div><div class=""> I've seen some Twitter messages that say AlphaFold might handle 2000 amino acids if you have say 4 GPUs and allow it to use memory from all of them and possibly do other tricks. But the limitation is that graphics processors have only so much memory and AlphaFold wants a lot, and more for larger sequences. So I don't think it is possible to compute a longer sequence as a single structure currently. It certainly is possible to combine the AlphaFold 1400 amino acid chunks in more sensible ways trying to avoid clashes but I don't have time to pursue that.<br class=""><div><br class=""></div><div> I figured you might not have wanted to mention your protein, but if you say it has 5005 amino acids then the cat is out of the bag.</div><div><br class=""></div><div><span class="Apple-tab-span" style="white-space:pre"> </span>Tom</div><div><br class=""><blockquote type="cite" class=""><div class="">On Sep 9, 2021, at 3:39 PM, Yunsik Kang <<a href="mailto:kangy@ohsu.edu" class="">kangy@ohsu.edu</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><meta charset="UTF-8" class=""><div class="WordSection1" style="page: WordSection1; caret-color: rgb(0, 0, 0); font-family: Helvetica; font-size: 12px; font-style: normal; font-variant-caps: normal; font-weight: normal; letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; white-space: normal; word-spacing: 0px; -webkit-text-stroke-width: 0px; text-decoration: none;"><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Hi Tom,<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Thank you so much! It is great that I inspired you to write this command.<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Since I have you (and I am no expert in structural biology), do you think alphafold will soon update larger proteins? Is there still a limitation? On your Youtube videos you guys state after 700 aa the system crashes a lot.<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">If I know a protein that perhaps might have a similar structure to my protein would it help resolves these clashing problems?<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">As you can see I tried to hide what my protein of interest was but it seems there are not a lot of 5005 amino acid proteins =).<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Thank you again!<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Yunsik<o:p class=""></o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div class=""><div style="border-style: solid none none; border-top-width: 1pt; border-top-color: rgb(225, 225, 225); padding: 3pt 0in 0in;" class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><b class="">From:</b><span class="Apple-converted-space"> </span>Tom Goddard <<a href="mailto:goddard@sonic.net" style="color: purple; text-decoration: underline;" class="">goddard@sonic.net</a>><span class="Apple-converted-space"> </span><br class=""><b class="">Sent:</b><span class="Apple-converted-space"> </span>Thursday, September 9, 2021 3:17 PM<br class=""><b class="">To:</b><span class="Apple-converted-space"> </span>Yunsik Kang <<a href="mailto:kangy@ohsu.edu" style="color: purple; text-decoration: underline;" class="">kangy@ohsu.edu</a>><br class=""><b class="">Cc:</b><span class="Apple-converted-space"> </span>ChimeraX Users Help <<a href="mailto:chimerax-users@cgl.ucsf.edu" style="color: purple; text-decoration: underline;" class="">chimerax-users@cgl.ucsf.edu</a>><br class=""><b class="">Subject:</b><span class="Apple-converted-space"> </span>[EXTERNAL] AlphaFold model for large proteins<o:p class=""></o:p></div></div></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Hi Yunsik,<span class="Apple-converted-space"> </span><o:p class=""></o:p></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> Inspired by your question and Tristan Croll's comment that the AlphaFold database has human proteins longer than 1400 amino acids computed as separate 1400 amino acid chunks I made a ChimeraX command "bigalpha" that loads and aligns these chunks.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><a href="https://rbvi.github.io/chimerax-recipes/big_alphafold/bigalpha.html" style="color: purple; text-decoration: underline;" class="">https://rbvi.github.io/chimerax-recipes/big_alphafold/bigalpha.html</a><o:p class=""></o:p></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">I attach two images and a PDB model made by running that command in ChimeraX for 5005 amino acid transmembrane protein<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Q2LD37 | K1109_HUMAN Transmembrane protein KIAA1109 OS=Homo sapiens OX=9606 GN=KIAA1109 PE=1 SV=2<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">and also here are a few other examples I looked at yesterday.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><a href="https://twitter.com/UCSFChimeraX/status/1435870388043411458" style="color: purple; text-decoration: underline;" class="">https://twitter.com/UCSFChimeraX/status/1435870388043411458</a><o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><a href="https://twitter.com/UCSFChimeraX/status/1435760774824169474" style="color: purple; text-decoration: underline;" class="">https://twitter.com/UCSFChimeraX/status/1435760774824169474</a><o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><a href="https://twitter.com/UCSFChimeraX/status/1435859111053193216" style="color: purple; text-decoration: underline;" class="">https://twitter.com/UCSFChimeraX/status/1435859111053193216</a><o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Keep in mind that the pieces of these models are not aligned in a reliable way and probably clash badly with each other because AlphaFold did not compute them as part of one structure. So these structures should only give you a very rough idea about the protein.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> Tom<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">This is the confidence coloring determined by AlphaFold, red low, blue high confidence. To reproduce this color using ChimeraX daily build open the PDB model and type command "color bfactor #1 palette alphafold". (The confidence value is saved as the bfactor in the PDB file).<o:p class=""></o:p></div></div></div></div><div class=""><br class=""></div><div class=""><div class=""><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Different AlphaFold chunks have different colors and chain identifiers in the PDB model.<o:p class=""></o:p></div></div></div></div><div class=""><br class=""></div><div class=""><div class=""><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div></div></div><div class=""><div class=""><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><br class=""><br class=""><o:p class=""></o:p></div><blockquote style="margin-top: 5pt; margin-bottom: 5pt;" class=""><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">On Sep 8, 2021, at 2:45 PM, Yunsik Kang via ChimeraX-users <<a href="mailto:chimerax-users@cgl.ucsf.edu" style="color: purple; text-decoration: underline;" class="">chimerax-users@cgl.ucsf.edu</a>> wrote:<o:p class=""></o:p></div></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div><div class=""><div class=""><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Hello,<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">My name is Yunsik Kang, and I am a postdoc in Marc Freeman’s lab at the Vollum Institute.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">I would love to use ChimeraX to predict the structure of my protein of interest. I watched all the YouTube videos and tried to run the program.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Unfortunately, my protein is 5005 amino acids in humans and 2958 aa in yeast. I get a message “<span style="font-size: 10.5pt; font-family: "Courier New"; color: rgb(33, 33, 33); background-color: white;" class="">Please use the full AlphaFold system for long sequences.”</span><o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">My question is what is the best way to approach this problem? Should I cut the protein in half and run the program? In one of the videos, it mentions after 700 aa it will have problems. Will it work if I get Colab-Pro? Or would the server crash no matter what.<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">I am not a structural biologist, but I hope the structure can help be predict me with my research. <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Thank you,<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class="">Yunsik<o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div><div class=""><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""> <o:p class=""></o:p></div></div></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><span style="font-size: 9pt; font-family: Helvetica, sans-serif;" class="">_______________________________________________<br class="">ChimeraX-users mailing list<br class=""></span><a href="mailto:ChimeraX-users@cgl.ucsf.edu" style="color: purple; text-decoration: underline;" class=""><span style="font-size: 9pt; font-family: Helvetica, sans-serif; color: rgb(149, 79, 114);" class="">ChimeraX-users@cgl.ucsf.edu</span></a><span style="font-size: 9pt; font-family: Helvetica, sans-serif;" class=""><br class="">Manage subscription:<br class=""></span><a href="https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users" style="color: purple; text-decoration: underline;" class=""><span style="font-size: 9pt; font-family: Helvetica, sans-serif; color: rgb(149, 79, 114);" class="">https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users</span></a><o:p class=""></o:p></div></div></blockquote></div><div style="margin: 0in 0in 0.0001pt; font-size: 11pt; font-family: Calibri, sans-serif;" class=""><o:p class=""> </o:p></div></div></div></div></div></blockquote></div><br class=""></div></body></html>