#protein structure

[hellsite-proteins]

AlphaFold Nobel Prize!

Hey everyone :) this isn't a structure, but there is some protein news that is pretty relevant to this blog that I felt I had to share. This article gives a nice overview of AI-predicted protein structures and what sorts of things they can do for research. It's not too long, and I recommend taking a look

If you've been seeing my posts for any amount of time, I've absolutely given you a flawed view of how useful AF can be. Experimentally determining protein structures is a demanding and difficult process (I've never done it, but I've learned the overview of how x ray crystallography works, and I can only imagine how much work it would take). AI-generated structures are not going to make structural biology obsolete, but they are massively helpful in making predictions that go on to guide further research.

While in many fields (especially creative areas like art and writing) AI has significant ethical concerns, I feel like this sort of use of AI in science is an overwhelmingly positive thing. The data used to train it is publicly available, and science works by building on the work done by those before us. Furthermore, while AI may not be great at generating new ideas or copying humans, it is very good at sorting large amounts of data and using it to make predictions. It's more akin to very complicated statistics than an attempt at the Turing test, and in this case it is a valuable tool to expand the ways we can do science!

[hellsite-noobteins]

raw input: penis filtered input: PENIS it's just a wibble, not much else to say i think?

stick | cartoon | surface

colored by pLDDT

[cbirt]

OpenFold, an artificial intelligence (AI) research consortium, has announced the release of two new tools that aim to improve protein structure prediction: SoloSeq and OpenFold-Multimer. These open-source tools represent important advances in integrating protein language models with structure prediction software, as well as modeling protein complexes more accurately.

The SoloSeq model developed on Amazon Web Services (AWS) emerges as a groundbreaking protein LLM/structure prediction AI tool. It holds the distinction of being the inaugural fully open-source model in this category, offering critical training code. Now, organizations can leverage this code for fine-tuning or training new models with their proprietary data, marking a pivotal step towards collaborative advancements in the field.

The first tool, SoloSeq, combines OpenFold’s existing protein structure prediction capabilities with a new protein large language model (LLM). This integration eliminates the need for a separate pre-processing step to generate a multiple sequence alignment (MSA) that is required by OpenFold and other structure predictors like AlphaFold.

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[er-cryptid]

Intrinsic Membrane Proteins

Patreon

[bpod-bpod]

Building a Sperm

Combining protein structure predictions with cryoelectron tomography reveals proteins – novel and known – their structures, interactions and locations in intact mammalian sperm

Read the published research paper here

Image from work by Zhen Chen and colleagues

University of California San Francisco, San Francisco, CA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Cell, October 2023

You can also follow BPoD on Instagram, Twitter and Facebook

[hellsite-proteins]

mushrooms are weird and vegetables are a social construct

letter sequence in this post matching protein-coding amino acids:

HnestlyiarrethattmatesgetalltheflackfrnteingavegetaleecasetheyretechnicallyafritwhenAThereareatnffritsthatgetcategrisedasvegetalesLikethisalsappliestpmpkinssqashesandccmersThefckingmshrmsarestandingthereattheackfthecrwdinthiswitchtrialtryingtlkincnspicsecasetheysmehwgtintthevegetaleclwithnfckingcntrversydespitethefactthattheyrentevenplants

protein guy analysis:

technically, there is some (unreliable) secondary structure to this mess, but you would barely believe it if you only saw the surface. disordered loops make up a good portion of the structure and separate most of the more ordered-looking elements from each other. the confidence is not high enough anywhere to convince me that this is anything other than an abomination of brownian motion. i have no idea what this would do to anything else it may interact with, but if you've ever seen an illustration of the inside of a cell that makes any effort to represent molecular crowding (there are some really beautiful illustrations out there!), then you too can share my morbid curiosity at what could potentially go wrong.

predicted protein structure:

cartoon representation

surface representation

Honestly bizarre that tomatoes get all the flack for “not being a vegetable” because they're technically a fruit when:

A) There are a ton of fruits that get categorised as vegetables. Like this also applies to pumpkins, squashes and cucumbers.

B) The fucking mushrooms are standing there at the back of the crowd in this witch trial, trying to look inconspicuous because they somehow got into the vegetable club with no fucking controversy despite the fact that they're not even plants.

[hellsite-proteins]

Hi, im sorry if this violates no nsfw but i thought i might try coz its been an old meme; delete if you dont want to ans it, no pressure!

I've come to make an announcement: Shadow the Hedgehog's a bitch-ass motherfucker. He pissed on my fucking wife. That's right. He took his hedgehog fuckin' quilly dick out and he pissed on my FUCKING wife, and he said his dick was THIS BIG, and I said that's disgusting. So I'm making a callout post on my Twitter.com. Shadow the Hedgehog, you got a small dick. It's the size of this walnut except WAY smaller. And guess what? Here's what my dong looks like. That's right, baby. Tall points, no quills, no pillows, look at that, it looks like two balls and a bong. He fucked my wife, so guess what, I'm gonna fuck the earth. That's right, this is what you get! My SUPER LASER PISS! Except I'm not gonna piss on the earth. I'm gonna go higher. I'm pissing on the MOOOON! How do you like that, OBAMA? I PISSED ON THE MOON, YOU IDIOT! You have twenty-three hours before the piss DROPLETS hit the fucking earth, now get out of my fucking sight before I piss on you too!

tbh i'm not going to be super strict about the no nsfw thing, but i also don't entirely trust the internet and wanted to make sure no one would submit anything truly vile. this is more comedic than anything else though, so you're all good!

letter sequence in this ask matching protein-coding amino acids:

IvecmetmakeanannncementShadwtheHedgehgsaitchassmtherfckerHepissednmyfckingwifeThatsrightHetkhishedgehgfckinqillydicktandhepissednmyFCKINGwifeandhesaidhisdickwasTHISIGandIsaidthatsdisgstingSImmakingacalltpstnmyTwittercmShadwtheHedgehgygtasmalldickItsthesiefthiswalnteceptWAYsmallerAndgesswhatHereswhatmydnglkslikeThatsrightayTallpintsnqillsnpillwslkatthatitlksliketwallsandangHefckedmywifesgesswhatImgnnafcktheearthThatsrightthisiswhatygetMySPERLASERPISSEceptImntgnnapissntheearthImgnnaghigherImpissingntheMNHwdylikethatAMAIPISSEDNTHEMNYIDITYhavetwentythreehrsefrethepissDRPLETShitthefckingearthnwgettfmyfckingsightefreIpissnyt

protein guy analysis:

if you've been here long enough or have a general idea of what proteins are supposed to look like, i'm sure you could write this analysis from looking at the picture for about two seconds. all i have to say is this: why is it so spread out??? the answer, of course, is that all of the many polar and charged residues are way too hydrophilic to make anything real, and instead are just flopping around uselessly with all the water. proteins were never meant to have this much entropy, and this chaos is downright infuriating

predicted protein structure:

[hellsite-noobteins]

the missile is very tired. he is eepy. the missile has had a very long day of splashing bandits and wants to take just a small sleep. he eeby and neebies to sleebie. mibsile sleepy and need bed by time. the missile is currently experiencing critical levels of being a sleehjy little guy and needs to go to beb. he is retired and needs to slep. just a little sleejing time as a treat. mibsilelelele neebs to slek for twired boyo. just a lil guy. mibsipaleebeelee needs his beaty sleep. look at him go! he yawn bib cause he skeegy. neebs to falafel asleep. ni ni time. goodnight, mr the missile.

raw input: ↑ filtered input: themissileisverytiredheiseepythemissilehashadaverylngdayfsplashinganditsandwantsttakestasmallsleepheeeyandneeiestsleeiemisilesleepyandneededytimethemissileiscrrentlyeperiencingcriticallevelsfeingasleehylittlegyandneedstgteheisretiredandneedstslepstalittlesleeingtimeasatreatmisileleleleneestslekfrtwiredystalilgymisipaleeeeleeneedshiseatysleeplkathimgheyawnicaseheskeegyneestfalafelasleepninitimegdnightmrthemissile theres a shit ton of alpha helices and a few beta sheets, it looks mostly orange, kinda stringy around the edges, kind of standard for a peptomination. yet, i somehow feel like it's on the good side of standard? although from a certain angle theres like. a hole. why is there a hole did the missile do that

cartoon | surface cartoon hole | surface hole

colored by pLDDT

[cbirt]

Centuries after the first proteins were identified and characterized, their complexity proves a challenge for scientists all over the world. Their creation, evolution, and many variations are questions for which we have only just begun to uncover the answers. A new bioinformatics tool has now been developed that can provide researchers with a way to analyze data and map protein sequences and structures on a large scale. This has important implications for protein modeling and sequencing technologies.

Genomes provide the template on which all life is created and maintained. Despite the high accuracy of DNA replication mechanisms found in living organisms, certain mutations can still occur and be passed on. Such mutations can change the function and structure of the protein that the gene is supposed to encode. Nearly all Mendelian diseases are caused by variations in the proteome.

In lieu of the time-consuming and exhaustive process of determining protein structures and mutations in the lab, researchers have now turned to bioinformatics as an alternative method to quickly and cheaply generate highly accurate and precise protein structure models. Many protein modeling tools have been developed to predict mutations and their impact with as much accuracy and precision as possible. The majority of such tools use only protein sequencing information from both the protein as well as its variants in order to produce results. While such a method is advantageous in that it is applicable to nearly all genetic mutations, they don’t account for the structure of the mutated variants, resulting in a loss of valuable information that can be garnered from taking the proteins’ 3-dimensional structures into account. This is especially important as it allows for distinguishing between mere correlations in mutation occurrence and causative variations. Hence, the results obtained through such methods may not be as accurate or precise.

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[hellsite-proteins]

letter sequence in this post matching protein-coding amino acids:

IustthinkitwouldefunnytoswitchthingsupandleadwithpopularfarrightonlineloggeroanRowlingonceinawhile

protein guy analysis:

this is a short one, but we did manage to get a bit of a beta sheet as well as a short helix! as always, still mostly loops and none of this is really trustworthy but i'm just excited to see some sort of secondary structure. for what its worth, i think this looks pretty neat

predicted protein structure:

I just think it would be funny to switch things up and lead with "popular far-right online blogger, Joan Rowling" once in awhile.

[hellsite-proteins]

i dont have a post but can you do this

heres the transcript

“Linda? What the fuck? Are you some fucking office secretary who just happens to be a middle aged white woman well into her 30s with a fucking demon of a child? Why in the ever loving shit did your parents name you Linda??? Like Linda is just Karen but somehow even more fucking stereotypical!”

peak writing

i'm not sure if this is a reference to anything or just thoughts on the name linda, but in my personal experience linda is just the boomer version of karen.

letter sequence in this ask matching protein-coding amino acids:

LindaWhatthefuckAreyousomefuckingofficesecretarywhousthappenstoeamiddleagedwhitewomanwellintoherswithafuckingdemonofachildWhyintheeverlovingshitdidyourparentsnameyouLindaLikeLindaisustKarenutsomehowevenmorefuckingstereotypical

protein guy analysis:

this was one of the rare structures that actually started to look worse as it was forming, and left me with a vile, unapproachable mess. i genuinely do not understand what rules the software had to break to even give me a pdb file, because there are side chains seemingly overlapping with each other and with the backbone. sure, no two atoms have their nuclei in the same space, but the bonds are so mangled that this could never stably exist. and this is even after the protein apparently severed some of the peptide bonds to make everything fit. apparently the rage against linda is strong enough to make electrons stop existing. this made me so mad i completely forgot that this travesty has some real alpha helices, if only to mock me. i am so upset that i had to look at this with my own eyes

predicted protein structure:

cartoon representation of the main chain

all side chains shown as sticks

close up of the center of the protein (so you can understand my pain)

[hellsite-noobteins]

raw input: [the vaporeon copypasta]

filtered input: [the vaporeon copypasta but without the numbers, punctuation, spaces, and the letters b, x, j, z, o, & u. i'm not putting it here you can't make me]

a nice amount of secondary structure in the center, even including a few beta sheets! shame about the absolute spaghetti outside and through it. also 2 of the alpha helices look... crimped, in a word. a distressing peptomination for a distressing string of text. good thing neither are real like look how fuckign oragne it is. the surface view kinda looks like one of those things you get by pouring molten metal in an anthill and waiting for it to cool jesus fucking christ

(also. did you know ChimeraX has a Spin Movie feature? because i didn't)

cartoon | surface

colored by pLDDT

[hellsite-proteins]

Featured Protein: Bacteriorhodopsin

this fantastic protein was suggested by @imperialinquisition, and i'm so excited i finally got around to putting together some information about it!

this protein is found in archaea – specifically Halobacterium salinarum, which are halophilic (live in extremely salty environments) obligate aerobes (need oxygen to function). it has 7 transmembrane domains and is an analog to human rhodopsin (a G-protein-coupled receptor protein in the rod cells of our eyes *note: bacteriorhodopsin is NOT a G-protein-coupled receptor, but is still in the 7TM receptor family) and forms distinct purple coloured parts of the cell membrane. this protein is also the source of a lot of interest from an engineering and biotechnology perspective.

this is one of several types of proton pumps, which transport protons across a cell membrane against an electrochemical gradient. however, the feature that makes this one so interesting is that it is powered by sunlight. when a photon of light is absorbed, all-trans-retinal (one molecule attached to each of 3 protein chains) is isomerised to 13-cis-retinal. this induces conformational changes in the rest of the protein through a 9-stage photocycle, altering the pKa values of a few conserved residues and allowing one proton to be transferred outside the cell. through this action, the inside of the cell is made 10,000-fold more basic than outside the membrane! this proton gradient is used to power ATP synthase, making most of the cell's ATP

sources:

i wasn't able to download a version of the structure with all three chains, but i found some cool images of the structure:

as always, if i made any mistakes, please let me know!

[hellsite-proteins]

sometimes i fear i sound a little too much like op when i tell y'all not to put the theoretical peptonominations into your living human bodies.

letter sequence in this post matching protein-coding amino acids:

asicallyithinkthegenerallefthmisifsmeneREALLYwantstheldthatsinsidefyrdyandtheyrelikeavampireradraclarsmesrtfmansqitthenthatspralykayadraclaandamansqitaremadefrremvingthingslikeldandswrdsfrminsideyrdythatsasicallyfineifsmethingwantstgetatyrldandtheyresaysmekindfmrdersarsrmayeareallyigfrgthatswheretheprlemsstarttariseareallyfrgisntmadefrremvingldandyrldknwsthiswhichiswhyitissvehementatwantingtstayINyrdyinsteadfcmingtnfrtnatelythiswillntdeterareallyigfrgecaseareallyigfrgisfllfthingslikepriesandvaleandqitealtfhatredanditwldREALLYratherliketreplaceanyandallfthsethingswithyrldandasicallyyanymeanspssileThesewrdsscanwithafantasticdegreefcnfidencecnsideringthattgethertheymakensenseatall

protein guy analysis:

this is one of the more deceptive structures, where from a certain angle it almost looks normal. there are lots of alpha helices, making up most of the protein. however, it is important to remember that proteins are three dimensional objects. upon rotating this structure 90º, we can see just how bad it really is. there are massive gaps between each helix, some of which are visible in the second surface representation. while the secondary structure is nice, acceptable tertiary structures remain elusive, and this is still gross to think about.

predicted protein structure:

cartoon representation

surface view 1 (matches above cartoon representation)

surface view 2

basically, i think the general rule of thumb is: if someone REALLY wants the blood that’s inside of your body, and they’re like… a vampire, or a dracula, or some sort of mansquito, then that’s probably okay. a dracula and a mansquito are made for removing things like blood and swords from inside your body. that’s basically fine.

if something wants to get at your blood, and they’re, say, some kind of murdersaurus, or maybe a really big frog, that’s where the problems start to arise. a really frog is not made for removing blood, and your blood knows this, which is why it is so vehement about wanting to stay IN your body instead of coming out. 

unfortunately this will not deter a really big frog, because a really big frog is full of things like prizes, and value, and quite a lot of hatred, and it would REALLY rather like to replace any and all of those things with your blood, and basically by any means possible.

[dr-afsaeed]

Would it be possible to kill bacteria without damaging their protein structure?

Would it be possible to kill bacteria without damaging their protein structure? There are several ways to kill bacteria without damaging protein structure or function. For example, consider the following frequent ones: 1. First, heat inactivation: Although heat may be used to destroy bacteria, it can also denature proteins if it is applied at too high a temperature for too long. However, some…