Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

作者： Chao E*1, Liqiang Dai*1,2, Jiaqi Tian3,4, Lin-Tai Da4, Jin Yu5,6,7 1Beijing Computational Science Research Center, 2Shenzhen JL Computational Science and Applied Research Institute, 3School of Medical Informatics and Engineering,Xuzhou Medical University, 4Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University, 5Department of Physics and Astronomy,University of California, Irvine, 6Department of Chemistry,University of California, Irvine, 7NSF-Simons Center for Multiscale Cell Fate Research,University of California, Irvine

简介：

Overview

This study aims to elucidate the structural dynamics of protein diffusion along DNA, utilizing the plant transcription factor WRKY domain protein as an exemplar. Both atomistic and coarse-grained molecular dynamics simulations were conducted to understand the one-dimensional diffusion process and its underlying mechanisms.

Key Study Components

Research Area

• Structural biology
• Molecular dynamics simulations
• Protein-DNA interactions

Background

• Diffusion of proteins along DNA is a crucial process for gene regulation.
• The WRKY domain protein serves as a model for studying transcription factors.
• Understanding the dynamics at an atomic level can provide insight into gene expression mechanisms.

Methods Used

• Atomistic and coarse-grained molecular dynamics simulations
• Markov state model construction
• Root mean square deviation and clustering analyses

Main Results

• Identified stepping motions of the protein along DNA at atomic resolution.
• Characterized the diffusion behavior over varying distances.
• Measuring time scales for transitions among identified states of protein-DNA complexes.

Conclusions

• This study demonstrates the kinetic mechanisms underlying protein diffusion on DNA.
• It highlights the importance of structural dynamics in biological processes such as gene regulation.

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