The Future of Medicine Computational Chemistry

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hi

today i’d like to talk to you about the

future of medicine computational

chemistry

um so just for a quick introduction hi

my name is sarah i’m a sophomore at los

altos high school

and i’m also a high school researcher at

aspiring scholars directed research

program

which is basically a program that allows

high schoolers to conduct their own

original research

and so there i’m a synthetic organic

chemist and what i work on is in the

drug discovery process

and that’s how i can tell you that the

drug discovery process takes a really

really long time

you start off with something called

analog design where you figure out what

you even want to make

and oftentimes people will want to make

libraries of compounds even up to like a

hundred

and then you go on to chemical synthesis

is and that’s like where you actually go

into lab

and you make whatever you said you

wanted to and this process takes a

really long time because

you have to start off with setting up

your reaction

and then after you set up your reaction

you have to purify it and finally you

have to characterize it

and these three steps can take up to

weeks

but then you combine the fact that

perhaps he said that you wanted to make

100 compounds in the beginning

you have to do this process over and

over again 100 times

and oftentimes this process takes up to

years to even complete your compound

library

and that’s barring any complications

and finally after you’ve spent perhaps

two to three years making your library

of compounds

you can finally test it and imagine how

disappointing it is if you spent two to

three years

working hard to make all your compounds

and then you find out that none of them

work

obviously this process is highly

inefficient because we see this happen

all the time and that’s where

computational chemistry can step in

computational chemistry can pre-screen

our compounds before we actually go into

the lab

and synthesize them and spend inordinate

amount of times

trying to make them and finally test

them

and so to do this we use computer models

for drug discovery

it starts off with de novo molecular

design which is almost analogous to the

analog design of the traditional drug

discovery process and it’s basically

where you

figure out what you want to screen then

you go on to something called density

functional theory and this is something

you can just download onto your computer

it’s completely open source

and you just plug in your molecule

through there and it comes out and it’s

completely optimized it’s like it would

be in the real environment

then after that you can use something

called molecular docking where you see

how your compound interacts with its

target

so for example if your compound’s

supposed to interact with the protein

this molecular docking can first of all

show you the orientation of it

but second of all it can tell you how

well this

compound would bind to the protein and

that’s really powerful

because if your compound binds really

really well to that protein

then you can basically say hey this is

actually worth synthesizing

but if it doesn’t bind very well to the

protein in the first place you don’t

want to be spending those years

making it and then finally you can do

something called a molecular dynamic

simulation

and this just shows you a real-time

simulation of your protein against your

compound

and this is really cool because you can

see perhaps your protein

folding or something and all of this

just goes to show that there are so many

computational techniques to help you

refine the drug discovery process

and so at our lab we have this 26 core

server which we use to screen 400

compounds to find a treatment for

covid and we basically just used those

400 compounds and we plugged them into

the computational chemistry process

and so here are a couple articles from

the stars cup 2 outbreak a year ago and

i think it’s really noteworthy to

mention that we actually started our

research

on kovid right at the outbreak of the

pandemic

and so even though no one was allowed to

be anywhere in person we were able to

continue our research

because all of our research was now

stored on our computers

and so if you want to figure out how to

cure covid you first have to understand

how covid works in your body

and you can kind of think of it like

this it’s like a long chain of events

and at the end of it covet proliferates

inside your body making you sicker and

sicker

but if we cut off one of the links to

those chains

covid won’t be able to grow through this

process and it’s not going to be able to

proliferate

and so that’s exactly what we did we cut

off this process right here

where there’s an enzyme in your body

called the main protease and it binds to

the covid

protein and since we can stop that

process

we can stop covid from being able to

proliferate inside your body and so to

do that

this is an example of our inhibitor and

the bottom thing is basically the

protein that we were trying to inhibit

and you can kind of think of this as a

door stopper our inhibitor is a door

stopper

and it’s permanently stuck there so that

covid can no longer enter it can no

longer bind with the protein

because our inhibitors already stuck

there

and so to do this we actually use

computer models for drug discovery

to test whether or not our inhibitors

would actually work before

we went into lab and synthesized them so

first we start off with some biological

inspiration for

our protein so this is the native

compound that binds

to our enzyme and we just militarize

that so this is basically the de novo

molecular design

portion of the computational chemistry

process

and then after that we plugged it into

the rest of the steps so the density

functional theory and the molecular

docking

and once we did that we identified our

hit compounds

so you can see here these are our two

best compounds and you can judge that

because they have the two best binding

affinities

to our covid enzyme and because of this

we have cut down our library of 400

compounds

to simply two and synthesizing going

through the traditional drug discovery

process

with 400 compounds might have taken us

even 10 years

but two compounds could take us a matter

of months and not only that it took us

only two months to even um screen them

on the computer

and so i just really really want to

emphasize how cool computational

chemistry is

not only that it’s improving the drug

discovery process

by making it so much faster and so much

more efficient but the fact that

it is so accessible the fact that

teenagers like me and my friends are

able to use this program

to find treatments for covid really mean

something and i hope

that computational chemistry will

improve the future of medicine

by not only making it more efficient but

by making it more accessible

and creating a safer world for everyone

thank you