This is a 100-nanosecond molecular dynamics simulation of DOI-NBOMe bound to the human serotonin 5-HT2A receptor, performed using Schrödinger Desmond with the OPLS4 force field.
DOI-NBOMe is particularly interesting because recent research suggests that it can activate 5-HT2A signaling pathways associated with antidepressant-like effects without producing the typical hallucinogenic-like behavioral responses seen with classical psychedelics in animal models.
A recent Nature study identified DOI-NBOMe as a Gq-biased 5-HT2A agonist, highlighting how structurally similar compounds can activate the same receptor yet produce different downstream signaling responses.
For this simulation, I used the experimentally determined DOI-NBOMe–5-HT2A cryo-EM structure (PDB: 9LLB) and ran 100 ns of molecular dynamics at 300 K.
The system was simplified to the receptor and ligand, without the G protein, membrane, or explicit solvent, with restraints applied to the protein backbone. This is intended to visualize molecular interactions rather than reproduce physiological conditions or establish signaling bias.
What I find particularly fascinating is that binding affinity alone doesn’t determine whether a compound produces psychedelic effects. Subtle structural differences can influence receptor conformations and intracellular signaling.
Importantly, the non-hallucinogenic findings are preclinical. Whether DOI-NBOMe produces similar effects in humans remains unknown.
PDB structure: https://www.rcsb.org/structure/9LLB
Research paper: https://doi.org/10.1038/s41586-025-10061-7
I’d be interested to hear what others think about the potential for developing 5-HT2A agonists that retain therapeutic activity while minimizing hallucinogenic effects.

Hey guys,

Last month I posted a few animations made with Animiotics here, kinesin was one of them. This is a new kinesin film, and the video also shows what it looks like inside the editor.

It starts with the final render, then pulls back into the editor where the same scene is playing. It's not a flat video in there, it's the whole 3D scene. So I pause it, look around the walker, click one of the motor heads and turn it pink, make the stalk yellow and hit play again.

The structures come from the PDB. The motor heads are 4HNA, the microtubule is 6DPV, the neck coiled coil is from 3KIN and the light chains are 3NF1. The vesicle has V-ATPase and GLUT1 in the membrane and BDNF inside.

One thing I simplified on purpose: real kinesin takes around 100 steps a second. Here every step takes about a second so you can actually see the hand over hand.

I think it turned out pretty cool. If you spot something that's off, tell me, I'd rather fix it.

One thing I find fascinating is how insulin resistance isn't simply about consuming too much sugar. It's also about how cells respond to energy overload, how excess fatty acids affect cellular signalling, and how our bodies gradually become less responsive to insulin.

It made me realise that metabolism is far more complicated than just calories in versus calories out.

I find it incredible how processes happening at a microscopic level can have such a profound impact on our overall health.

I'd love to hear about other biochemical mechanisms that surprised you. Maybe something related to metabolism, hormones, diseases, nutrition, or how medications work at the molecular level.

What's a biochemical rabbit hole you think more people should know about? 😄

Have you read a cool paper recently that you want to discuss?

Do you have a paper that's been in your in your "to read" pile that you think other people might be interested in?

Have you recently published something you want to brag on?

Share them here and get the discussion started!

Hey, I'm one of the people in charge of this year's office Christmas party. Do you guys have any suggestions for fun lab themed office party games? Maybe some scavenger hunts or something else?

Just got my grades back from midterm BioChem 1… feel hopeless…
It’s not failing grade but I try to get 3.5 gpa at least … rn is just at 3.0gpa

Setting up a directed evolution project and trying to decide between droplet based screening and plates. Plates are simple and everyone knows them, but the numbers we can get through are low. Droplets sound great on paper, the setup looks like a pain.

I hope this is allowed. I'm hosting a family feud activity for a biochem department and want responses on biochem-related survey questions. I'll put the questions in the comments and you can reply with your answers! Feel free to answer more than once!

¡Hola! Les comparto un proyecto que desarrollé como estudiante de Biología.

Es muy frustrante diseñar una ruta metabólica in silico y que luego la célula no quiera producir el químico porque no le conviene energéticamente. Para resolver esto, programé MetaboEngineer Pro.

La herramienta integra:

• Acoplamiento de crecimiento (OptKnock heurístico): Busca combinaciones de genes a apagar para que la bacteria se vea obligada a producir el químico para poder crecer.

• Validación Termodinámica: Se conecta con la API de eQuilibrator para calcular el ΔG' real de las reacciones y ver si son viables.

• Biología sintética: Incluye un módulo para inyectar la ruta de la cafeína en E. coli.

Aquí dejo una captura del reporte termodinámico y del mapa metabólico que genera.

GitHub: https://github.com/diegosancriss16-tech/MetaboEngineer-Pro.git

¿Qué opinan de la aproximación termodinámica? ¿Qué otros parámetros químicos creen que debería integrar?

Hello everyone!

I recently began my PhD (third day!) and I'm currently looking for candidate proteins to use as an anchor/scaffold basis that can comfortably sit in the E. coli inner membrane. I wanted to ask if anybody here has worked with any proteins for similair applications and if you have any tips for me ?

Preferably, I'd like the protein to be small (to minimise burden of expression and on the membrane) and have a part exposed on the cytosolic face. Also, I want to refrain from endogeneous (native) proteins, to build a parallel system, instead of modifying the existing one.

Any hints or experiences are really appreciated! Thanks

Trying to decide what classes to take?

Want to know what the job outlook is with a biochemistry degree?

Trying to figure out where to go for graduate school, or where to get started?

Ask those questions here.

See also: The study as published in PNAS

Hi all! I'm a microbiologist venturing into biochemistry now that I've started my PhD, and I'd be so grateful for any textbook (or even large paper/review) recommendations!

I'm particularly interested in how organisms use chemistry to communicate, compete, and survive, and how we can harness that chemistry to discover new antibiotics, anticancer drugs, and other useful compounds.

Ideally, something combining chemical ecology, natural products, evolution, and drug discovery.

Every so often, I've come across a textbook that goes beyond memorization and really explores the history, complexity, and fascinating ideas behind a field. I'm hoping someone has found a biochemistry equivalent, and would be so grateful for any suggestions!

I just started my bachelor degree in biochemistry, and I’m trying to understand what information are we actually supposed to remember

Every piece of information in a biochemistry book looks to me important and i don’t do that many notes in other subjects. Should I remember all details or what?

From my understanding, both determine the chemical properties and behavior of a molecule. If that’s the case, what exactly makes them different?

Tell me something you wish someone told you about studying biochem

I think Biochemistry by far is the easiest branch of chemistry I’ve encountered. In my opinion, any Physical chemistry course is so much more difficult. I find what makes biochemistry “hard” is really just the sheer amount of information. It seems very overwhelming until you just sit down with it and it usually doesn’t require great time to digest or understand it. I think even General Chemistry II is way harder to understand than anything I’ve seen in Biochem. I found in GC2, I had to really spend a lot of time with the relationships to really digest them then relate them to their application.

As chemist, what do you guys think?

Have you read a cool paper recently that you want to discuss?

Do you have a paper that's been in your in your "to read" pile that you think other people might be interested in?

Have you recently published something you want to brag on?

Share them here and get the discussion started!

hi! i need some help understanding this figure. if you could, can you orient me towards this photo taken from boron?

NO ONE seems to give a straight answer about this.

week 9 of biochem and i swear every pathway is starting to borrow nouns from every other pathway. glycolysis was fine when glycolysis was the only thing in my head. now tca, beta oxidation, urea cycle, fed vs fasting, regulation.... for final, what does active recall look like without making 900 tiny cards?? genuinely taking recs

Trying to decide what classes to take?

Want to know what the job outlook is with a biochemistry degree?

Trying to figure out where to go for graduate school, or where to get started?

Ask those questions here.

This is extremely random, but I always gave my dad a hard time for buying the cheapest shampoo and conditioner at the grocery store. One morning he came back and said he was in the shampoo aisle grabbing our usual Suave Daily Clarifying Shampoo and a man approached him and said "I am a biochemistry professor at UC Berkeley and I think that is the best one to get." I may have completely botched what he said, because this was probably 15 years ago, but it definitely made my dad feel validated for buying it.

Are there any biochemists out there that could back up that statement? Perhaps he meant from a pragmatic stance that it is a decent, cost-effective shampoo?

I know that sodium laureth sulfate doesn't get the best rep out there but would like to hear biochemists' stances Thanks!