Biomodeling: DNA-binding proteins (PCNA)

Intro

There are several well known DNA-binding motif proteins.
In those DNA-binding proteins, basic residues bind to
- Backbone phosphates: non-specific (e.g., RNA polymerase).
- Major grooves: motif-level, specific and relatively weaker (e.g., zinc finger, helix-turn-helix etc.).
- Minor grooves: single residue-level, specific and relatively stronger (e.g., histone, exonuclease etc.).
DNA-binding proteins diffuse along DNA to find the target sites!!!

You, S., Lee, H. G., Kim, K. & Yoo, J. Improved Parameterization of Protein-DNA Interactions for Molecular Dynamics Simulations of PCNA Diffusion on DNA. J Chem Theory Comput 16, 4006-4013 (2020). https://doi.org/10.1021/acs.jctc.0c00241
Blainey, P. C. et al. Nonspecifically bound proteins spin while diffusing along DNA. Nat Struct Mol Biol 16, 1224-1229 (2009). https://doi.org/10.1038/nsmb.1716
Kochaniak, A. B. et al. Proliferating cell nuclear antigen uses two distinct modes to move along DNA. J Biol Chem 284, 17700-17710 (2009). https://doi.org/10.1074/jbc.M109.008706

In Kochaniak et al., you can find the single-molecule measurements of a PCNA complex as a function of time, y(t).
Using y(t), we can calculate the mean-squared-displacement (MSD) curve.

Questions
- Diffusion coefficient of the protein complex?
- Translational vs. rotational?
What is the physical nature of the protein-DNA contacts?
- Visual inspection
- Radial distribution functions?
- What else?

In the Dropbox folder (PCNA), you can find a trajectory file.

For a 1D diffusion case, the diffusion coefficient is defined as MSD(∆ t)= 2D∆.t

A Python example.

https://stackoverflow.com/questions/31264591/mean-square-displacement-python

import numpy as np

# calculate COM of PCNA and put the z coordinates to zdata array.

r = np.sqrt(zdata**2)

diff = np.diff(r) #this calculates r(t + dt) - r(t)

diff_sq = diff**2

MSD = np.mean(diff_sq)