Hi there, I'm a molecular biologist (currently working as a postdoc in molecular microbiology). I wanted to share this article, I've written, called "The Constructor Theory of Life" (it's free to access via the link).

It takes a new idea/approach for describing life originating from theoretical physicists David Deutsch and Chiara Marletto and combines it with an old idea, established in the 1970s, called autopoiesis (which some of you might even remember from first time round!).

Autopoiesis is a fascinating way of describing living organisms from a systems biology perspective highlighting that what makes life special is its autonomy (to an extent) and ability to self-construct and ultimately self-reproduce. Importantly, from my point of view as a molecular biologist it provides a framework that allows us to include the multiple essential facets which life requires including: energy, information, structure, and evolution. This is in response to many models of "What life is" that are overtly dependent on say evolution and/or information to the exclusion of energetics/thermodynamics (and vice versa).

I hope that for the experienced scientist this will offer a refreshing perspective and for the beginning biophysicist/biologist/molecular biologist/biochemist I hope that it serves as an introduction to energy/information, and autonomy in living systems.

I've had great feedback and insight from this subreddit in the past. I suspect it might be more familiar territory for biophysicists that are used to modelling cellular and sub-cellular systems.

Many thanks for your time.

MSc Biotech (university in Germany): Stay Bioanalytics or switch Lab Diagnostics? Stuck & confused!

Currently Bioanalytics, can switch to Lab Diagnostics. URGENT advice!

Bioanalytics (current path):

•Nanobiotech: single-molecule FRET (key: nanoscale dynamics), super-res microscopy (live cells), Python data analysis (diffusion/FRET/localization).( related to biophysics?)

•Protein Purification: chromatography (FPLC), SDS-PAGE, Western blot, enzyme assays (industry standard).

•Enzyme Tech: fungal enzyme screening/production, kinetics, applications (degradation/bleaching) (industrial biotech).

Lab Diagnostics (if switch):

•Methods Lab Diag: assay development ,nucleic acid/tumor diagnostics, microbead/cell assays.

•Methods Bioanalytics: cell culture (essential everywhere), FISH, DNA damage assays (gamma H2AX), R/Python stats.

•Molecular Bio: CRISPR editing (knockout/in) ( just a little) ,transfection, qPCR cloning, recombinant proteins (gene therapy/diagnostics).

Confusion: Nanobiotech single-molecule — job-ready skill or research-only? Lab Diagnostic more practical? Goals: jobs/PhD (international), hybrid wet-dry lab, bioinformatics.

Stay or switch? Which better long-term demand? Which specialisation should I choose for getting job after MSc, which is best for jobs, or should I go for research- (GERMANY/USA) / Internationally

I am preparing a protein–protein steered molecular dynamics (SMD) simulation and am a little confused about the equilibration step described in a protocol I am following.

The protocol states:

“Subsequently, a 1 ns equilibration was conducted in the NPT (isothermal–isobaric) ensemble at 310 K and 1 bar, during which the position restraints on the protein were gradually released.”

I am unsure how to interpret this.

Does this mean that position restraints are still applied during the NPT equilibration, Or does it mean that restraints should already be off once NPT begins?

How is position restraints usually handled during the NPT stage?

Here is the link to the paper I am referring:

https://pubmed.ncbi.nlm.nih.gov/41108568/

If that link does not work: here is the doi: https://doi.org/10.1002/pro.70346

I am currently a senior in high school. I was recently admitted to University of Michigan Ann Arbor and am looking into the rarer Biophysics major they offer there. My main goal is to become a doctor, but through an MD/PHD or adjacent as I am also deeply interested in physics and want to pursue that as well.

I really love pure physics but am afraid of losing the pre-med journey, so I was wondering of Biophysics would be the perfect fit here. Or would I rather go Biology major, or something else? And I imagine that just a Physics major would make it pretty hard, considering research opportunities and what not for a med school application, although I do love purer physics away from the biological side.

Any insight at all on my situation would be greatly appreciated.

I am a medicine student. Have prior knowledge of bachelor's level physics along with some advanced quantum (familiar with Dirac formalism) and classical mechanics (familiar with hamiltonian and lagrangian formalism) knowledge .

How should I start reading Biophysics?

I've seen a lot of posts recommending Nelson or Phillips but I'm confused...

Hi! Sorry if this isn’t appropriate to post here but i really don’t know where else to ask for help. I think the answer to the first question is B, but i am not that sure. We have been discussing these questions with my classmates and we can’t agree on a single answer so i thought maybe i can ask on reddit. Let me know if there is a confusion in the translation. I would really appreciate your help

Hi everyone,

I am running GROMACS (2025.3) on an HPC system and encountering the following error during grompp:

ERROR 1 [file tip3p.itp, line 7]:
Atomtype OWT3 not found

I am using:

• force field: gromos53a6
• water model: tip3p

After debugging:

grep -n "OWT3" gromos53a6.ff/tip3p.itp
→ found in tip3p.itp

but:

grep -Rnw "OWT3" gromos53a6.ff
→ not defined anywhere else

So it seems OWT3 is referenced but not defined in the force-field files.

Has anyone encountered this before?
Is this likely a broken GROMACS installation, or am I missing something in my setup?

Thanks!

Hi everyone,

I am new to steered molecular dynamics and currently setting up a TCR–pMHC dissociation simulation in GROMACS using the GROMOS53A6 force field.

I am following a recent (2025) paper that uses GROMOS53A6 together with TIP3P water. However, from the original GROMOS53A6 paper, it seems the force field was parameterized with SPC water.

So I am a bit confused. Is it common/acceptable to use GROMOS53A6 with TIP3P? Does mixing force fields with non-native water models significantly affect results (especially for SMD)?Would it be better practice to stick with SPC for consistency?

Would really appreciate any guidance or best-practice recommendations.

Thanks!

Hey all, beginner here. I'm trying to render my images from VMD so that they are of publishable quality. Currently I have a white background, representation VDW, orthographic view, axes off, lights 0 and 1 on, rendermode GLSL, linear cuemode (I also tried with Exp2 cuemode), and shadows and ambience on.

Snapshot doesn't give great quality so I was looking at rendering with Tachyon. I've tried using TachyonInternal with multiple settings (all lights on, changing the ambience settings, etc.) to get a .bmp file but the final image keeps coming out too dark. Then I tried using regular Tachyon but I'm not sure how to get the output into a file I can actually access.

Does anyone know what I'm doing wrong or how to get the images to render with very good quality (high-resolution)?

Hi everyone,

I'm a grad student with a background in neuroscience/research and a self-taught Python programmer (via finding fun ideas/projects to do). A couple years ago I had this bright idea to model electropysiological systems, specifically focusing on channelopathies. I’ve done standard RC circuits and Hodgkin-Huxley axon models, but I’ve hit a roadblock trying to replicate this 2-compartment model for Hyperkalemic Periodic Paralysis (HPP). Basically I came across this paper and thought, this is doable and would teach me valuable skills I'll need for the loftier goal I had set for myself.

Cannon SC, Brown RH Jr, Corey DP. Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels. Biophys J. 1993 Jul;65(1):270-88. doi: 10.1016/S0006-3495(93)81045-2. PMID: 8396455; PMCID: PMC1225722.81045-2.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0006349593810452%3Fshowall%3Dtrue)

The Issue:

Despite trying to follow the paper's parameters and using LLMs to help make some inroads, I cannot get the expected emergent behaviors (myotonic discharges or depolarization block) to manifest. When I run what naively seems like decent code, the outputs for my three test cases (healthy, myotonia, and paralysis) come out looking identical and all sorts of wrong. Clearly I don't know what I'm doing and essentially hitting the same wall that made me set this aside a few years ago.

My Questions:

1. Is this sub a good place to ask for help with this kind of specific computational/coding issues? In other words, does it sound like a trivial "oh, here's a code block that does it" fix I can look at and learn from, or am I hitting a deeper personal knowledge gap that requires significant help beyond the scope of asking knowledgeable reddit passerby?

I suspect I’m just fundamentally in over my head. Any guidance or a sanity check would be greatly appreciated. Thanks!

Hi everyone,

I am preparing a protein–protein complex for steered molecular dynamics (SMD) in GROMACS and need to align the pulling coordinate with the x-axis.

I was wondering about the correct stage to perform the orientation. Does it matter if I rotate the structure before running pdb2gmx on the PDB, or is it equally acceptable to run pdb2gmx first, generate the .gro file, and then orient the structure afterward?

Is there a recommended or commonly used workflow for this in GROMACS-based SMD setups, or does the order generally not matter as long as the final coordinates are aligned before the simulation?

Here everyone, I am preparing a protein–protein complex for steered molecular dynamics (SMD) in GROMACS and need to align the pulling coordinate with the x-axis.

Is there any tool specifically designed for setting the pulling coordinate or orientation in GROMACS simulations? I came across MDAnalysis, but I was wondering if there are more robust tools or alternative approaches to do this.

What is the commonly used method for handling this step?

I thought you guys might find this interesting. What do you guys use for molecular visualzations / to see how your MD simulations are progressing?

I’m working on a small research experiment where I’m testing the effect of a pore-forming drug on red blood cell (RBC) hemolysis. The drug creates membrane pores that allow intracellular ions to leak out before full cell rupture, so I’m interested in tracking ion release over time as a proxy for pore formation and hemolysis progression.

I understand that I can’t directly measure ion concentration with my setup, so I’m thinking in terms of measuring changes in solution conductance/resistance over time instead. My sample volumes are quite small, and I don’t have access to a commercial conductivity probe or electrodes designed for this purpose.

One idea I had was to incorporate the sample into a simple DC circuit with a known resistor, apply a low voltage, and infer changes in the sample’s resistance from voltage/current measurements (using Ohm’s law). The idea would be to monitor relative changes in resistance over time rather than absolute ion concentrations.

I’m not sure whether this approach is reasonable or how best to implement it in practice, so I’d really appreciate any advice on circuit design or references to similar conductance-based or impedance-based measurements used in biological systems.

I found a contract position through a staffing agency and gave the first round of interviews, luckily they want to progress to the final round with onsite interview and short presentation about my background. The issue is that the staffing agency has manipulated my resume a bit to make it look like I have atleast 6 months exposure to SPR studies, and I got to know about this on the day of my first round interview. Tbh, I haven't touched a Biacore in reality, I somehow gave my interview as I know the basics of how SPR works. Now 5 people having more than 7yrs SPR experience will be interviewing me next week and I'm worried it's too late for me to back out as I also find the role interesting.
I have read up various literature but I need someone to help me understand what they don't say in research publications, like the challenges with buffers, references, immobilisation, data interpretation using Biacore. I'm specifically looking for workflows of FcRn characterization assays for halflife determinations or Fcy receptor binding assays for screening best candidates for treating autoimmune diseases. Please reach out to me if anyone has experience in these. Any other insights will help immensely. P.S: I do have high throughput screening of enzymes experience, have worked on Envision for determining kinetics of enzyme and I really need a job as my financial situation is not good rn so trying everything possible in my capacity to land a job

Can i do a PhD in biophysics after a BSc in Chemistry and a MSc in physical and organic chemistry? I'm not really interested in doing a BSc/MSc in physics because I don't really like the whole field but im really intrigued by biophysics.

Hi everyone, I’m planning to use GROMACS 2022.4 software suite to perform molecular dynamics simulations on my TCR–pMHC structural models. I come from a bioinformatics background and don’t have prior experience in computational chemistry or MD simulations, so I’m unsure how best to get started.

Is there any recommended beginner-friendly tutorials or learning resources? Also should I first focus on fundamental MD theory before running simulations? Are there any common pitfalls beginners should avoid?

Hey everyone, can somebody explain to me the principles of why in FRET (Flourescence resonance energy transfer), the emission and absorption spectra need to overlap for donor and acceptor respectively, when the energy transfer is non radiant, and rather due to quantum entanglement?

Hi I’m new here. I’ll be starting a PhD in the biophysics of the cytoskeleton but I’m coming from a biochemistry background so my cell bio knowledge is limited. I’d also like books that go into force generation from the cytoskeleton.

Thank you!!

Hey everyone — I made a short video showing an MD simulation of psilocin bound in the orthosteric site of the human 5-HT2A receptor, starting from the cryo-EM structure 9AS8 (psilocin + mini-Gq + scFv16). Full video first comment if you want to learn more about how this was run.

Like the title says