Probing the modulation in facilitated diffusion guided by DNA–protein interactions in target search processes

Many fundamental biophysical processes involving gene regulation and gene editing rely, at the molecular level, on an intricate methodology of searching and locating the precise target base pair sequence on the genome by specific binding proteins. A unique mechanism, known as ‘facilitated diffusion’...

Full description

Saved in:
Bibliographic Details
Published in:Physical chemistry chemical physics : PCCP 2024-07, Vol.26 (30), p.20296-20309
Main Authors: Thonnekottu, Diljith, Chatterjee, Debarati
Format: Article
Language:English
Subjects:
Chain dynamics
Deoxyribonucleic acid
Diffusion rate
DNA
Dynamics
Genetic modification
Modulation
Proteins
Search process
Three dimensional motion
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Many fundamental biophysical processes involving gene regulation and gene editing rely, at the molecular level, on an intricate methodology of searching and locating the precise target base pair sequence on the genome by specific binding proteins. A unique mechanism, known as ‘facilitated diffusion’, which is a combination of 1D sliding along with 3D movement, is considered to be the key step for such events. This also explains the relatively much shorter timescale of the target searching process, compared to other diffusion-controlled biophysical processes. In this work, we aim to probe the modulation of target search dynamics of a protein moiety by estimating the rate of the target search process, and the statistics of the search rounds and timescales accomplished by the 1D and 3D motions, based on first passage time (FPT) calculations. This is studied with its characteristics getting influenced by various given conditions such as, when the DNA is rigid or flexible, and when the target is placed at different locations on the DNA. The current theoretical framework includes a Brownian dynamics simulation setup adopting a straightforward coarse-grained model for a diffusing protein on DNA. Moreover, this theoretical analysis provides insights into the complex target search dynamics by highlighting the significance of the chain dynamics in the mechanistic details of the facilitated diffusion process.
ISSN:1463-9076
1463-9084
1463-9084
DOI:10.1039/d4cp01580k