Presenting one of my favorite manuscripts I've ever worked on: "Characterizing structural and kinetic ensembles of intrinsically disordered proteins using writhe" www.biorxiv.org/content/10.1... by Tommy Sisk, with a generative modeling component done in collaboration with @smnlssn.bsky.social - ThreadSky

paulrobustelli.bsky.social • 10 days ago

Presenting one of my favorite manuscripts I've ever worked on:

"Characterizing structural and kinetic ensembles of intrinsically disordered proteins using writhe"

https://www.biorxiv.org/content/10.1101/2025.04.26.650781v1

by Tommy Sisk, with a generative modeling component done in collaboration with @smnlssn.bsky.social

Comments

paulrobustelli.bsky.social•10 days ago

If want to use topology, geometry and Markov state models to describe the conformational ensembles and dynamics of IDPs (and who doesn't?) with a little deep learning spice, this one is for you.

So what is this writhe business? Writhe describes the orientations of curves in 3D space.

paulrobustelli.bsky.social•10 days ago

We're inspired by work in the late 70s by Harold Scheraga using differential geometry to describe polymer conformations (https://pubs.acs.org/doi/epdf/10.1021/ma60066a020) and a Michael Levit 1983 JMB classic (https://www.sciencedirect.com/science/article/pii/S0022283683801296?via%3Dihub) calculating writhe of protein conformations using discrete segments.

paulrobustelli.bsky.social•10 days ago

We set out to see if we can understand IDP ensembles and dynamics using writhe. Instead of using inter-residue distances (or contact maps), we're going to describe IDP conformations using "writhe matrices", that describe the crossings of all segments of a protein at a desired segment length

paulrobustelli.bsky.social•10 days ago

You can think of a writhe matrix as having a radial component that describes the distance between segments, with an additional angular component, that describes the relative orientations of each segment. It has the distance information of a contact map, with additional info on segment orientations

paulrobustelli.bsky.social•10 days ago

Here is an illustration of how to compute writhe in a geometric fashion. You can project the apparent crossings of two segments to define a spherical quadrangle, and use this the accurately calculate writhe. Tommy wrote a python package to do this real fast

https://github.com/paulrobustelli/Sisk_IDP_Writhe_2025

paulrobustelli.bsky.social•10 days ago

Polymers (and IDPs) have different timescale fluctuations at different length scales. We compare writhe matrices computed with different segment lengths for a folded conformation of HP35, and show that they are sensitive to different structural features. We analyze a folding trajectory of HP35...

Comments

Posting Rules

Reply