How in the HELL do you even begin designing novel enzymes?

>>8546165
There's a reason people study shit like this their whole lives. This is that reason.

>>8546165
By designing, do you mean de novo creation? If not rational site directed mutagenesis and directed evolution are currently in use to make enzymes better or to give them new functions

>>8546165
The same way you design any complex modifications with a top-to-bottom approach.
You a) experiment with small changes and b) identify reusable modules and recombine them. If you're confident with recombining modules, you start creating modified modules to suit your needs.

>>8546165
>>8546165
It looks like a clusterfuck but if you know your shit >>8546367
applies

Its all about patterns

>>8546165
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962183/pdf/CSBJ-2-e201209010.pdf

Since I have a biocatalysis exam on tuesday and I'm supposed to know some strategies ill type it out a bit for you

You got non-rational, semi-rational and rational

Non-rational you just have a bunch of random mutations in the gene that encodes for the enzyme, then you see what works by doing mass screening of substrates

Semi-rational is CASTing, basically you only randomize the genes that encode the active site of the enzyme

Rational you look at the structure and change amino acids according to what you think would fit your substrate

So what do you use the enzyme for?
>What is this even?

>>8546165
>how do you design a car if you dont know how a car works
really made me think

>>8546165
A lot of simulation and a lot of mutations and experimentations.
There's a lot of trial and error because it's just really hard working with such complex systems.

>>8546385
Best of luck on the exam, mate.

>>8546165
Yeah, wellcome to the real world.

>tfw I used to think "just brute force it lol molecular dynamics blaze it errday"
>turns out there's like a fucking googol of possible configurations
good luck with that biofags

>>8546816
thanks lad

gene editing?

>>8546165

Ask the guy who runs this lab: https://www.bakerlab.org/.

>>8547346
Aren't they the same people behind Foldit?

>>8546367
This is bad advice. Don't make small changes to an existing form, the effects will be too hard to track.
Instead start with a bare form, with no real functionality, and try to add functionality.

>>8547546

Indeed, they are.

>>8546851
It's not impossible...

>>8547233
how was tthe exam

>>8547634
>This is bad advice. Don't make small changes to an existing form, the effects will be too hard to track.
Instead start with a bare form, with no real functionality, and try to add functionality.

You sound like a CS major. At least take a class on proteins before opening your mouth nigger.

>>8547634

yeah i fully disagree with this opinion here

if you attempt to start with a bare form i'd really love to see your process for building up a final folded structure, particularly anything that isn't just a single polypeptide

you are better off making modifications to existing catalytic cores or surrounding, relevant regulatory subunits to achieve specific goals, based on something we have already seen done in nature

>>8547634
The only way TO do it is by making small changes to an existing form. Protein structure is really mysterious. You can't even look at an amino acid sequence and predict its folded structure (although there is a yearly competition where biophysicists/chemists meet up and try to predict structure from sequence to win a prize). The best we can do, and what I have experience in, is by doing base substitutions of existing proteins with plasmid vectors.

>>8550269

this is actually how we teach PTM and site-directed mutagenesis, props to you my friend

You use foldit.exe and shake!

>>8550316
keked

>>8547761
They're from the University of Washington? Is that good

>>8550373
It's not a kekable matter. I wish I had the time to participate in the fold-it project, but these days I'm too easily distracted by less enjoyable things.