Selected Publications

How transcription factors (TFs) recognize their DNA sequences is often investigated complementarily by highthroughput protein binding assays (modeled by the position weight matrix, PWM) and by structural biology experiments. Here, we propose and test a new modeling method that incorporates the PWM with complex structure data. We model the specific protein−DNA interactions, PWMcos, in terms of an orientation-dependent potential function, which enables us to perform molecular dynamics simulations at unprecedentedly large scales. We show that the PWMcos model reproduces subtle specificity in the protein−DNA recognition: during the target search in genomic sequences, PU.1 moves on highly rugged landscapes and occasionally flips on DNA depending on the sequence; the TATA-binding protein exhibits two remarkably distinct binding modes, of which frequencies differ between TATA-containing and TATA-less promoters. The PWMcos is general and can be applied to any protein−DNA interactions given their PWMs and complex structure data are available.
J. Chem. Theory Comput., 2018, 14 (7), 3877-3889.

The correlation between protein binding to DNA and DNA bending has been observed in many protein-DNA complex structures. These are, however, the correlation in static structures. Due to time and spatial resolutions in experiments, little is known on the dynamic coupling between protein binding and DNA bending. Here, armed with new simulation methods, we investigated the dynamic coupling between protein binding and DNA bending for a bacterial protein HU and 14 other proteins. The sliding of positively-charged HU on negatively-charged DNA is highly coupled with local DNA distortion, which is reminiscent of polaron in physics. In shorter time scale, HU was self-trapped in a locally bent DNA leading to pauses. Spontaneous relaxation in DNA shape resulted in the sliding mode.
J. Am. Chem. Soc., 2016, 138 (27), 8512–8522.

Recent Publications

  • Dynamic and Structural Modeling of the Specificity in Protein-DNA Interactions Guided by Binding Assay and Structure Data
    J. Chem. Theory Comput., 2018, 14 (7), 3877-3889.

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  • DNA sliding in nucleosomes via twist defect propagation revealed by molecular simulations
    Nucl. Acids Res., 2018, 46 (6), 2788-2801

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  • Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations
    PLoS Comp. Biol., 2017, 13 (12), e1005880

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  • Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics
    J. Am. Chem. Soc., 2016, 138 (27), 8512–8522.

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  • Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations
    Acc. Chem. Res., 2015, 48 (12), 3026–3035.

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  • Atomistic Picture for the Folding Pathway of a Hybrid-1 Type Human Telomeric DNA G-quadruplex
    PLoS Comput. Biol., 2014, 10 (4), e1003562.

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  • Localized Frustration and Binding-Induced Conformational Change in Recognition of 5S RNA by TFIIIA Zinc Finger
    J. Phys. Chem. B, 2013, 117 (50), 15917–15925.

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  • Specific Binding of a Short miRNA Sequence by Zinc Knuckles of Lin28: A Molecular Dynamics Simulation Study
    J. Theor. Comput. Chem., 2013, 12 (8), 1341015.

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  • Low Folding Cooperativity of Hp35 Revealed by Single-Molecule Force Spectroscopy and Molecular Dynamics Simulation
    Biophys J., 2012, 102 (8), 1944-1951.

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Simulation of coarse-grained protein in explicit water.

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At the beginning of 2018, I decided to design a template for my notes in 2018.

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Cheat Sheet for LaTeX mathematics.

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Build a Chatting bot for Wechat with the wxBot package.

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An example of using git-svn to organize code. Specially for git-lovers to use svn.

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Projects

py_sdvb

Yet another dictionary tool written in python. Allow regex.

esnippets

My snippets for Emacs yasnippet.

PyWMLogo

A simple tool to plot information content LOGO for PWM. Image format is svg.

pinang

This is a package consisting of several small handy tools for analyzing biomolecule structures (protein, RNA, DNA) and CafeMol MD trajectories.

respac_batch

Simple script to perform RESPAC calculations (including APBS) for coarse-grained protein charge distributions.

spacemacs_layers

My spacemacs configurations (init.el) and additional layer settings.

cafemol-mode

An Emacs major mode for editing CafeMol input file.

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