Simulation of coarse-grained protein in explicit water.
Selected Publications
Dynamic and Structural Modeling of the Specificity in Protein-DNA Interactions Guided by Binding Assay and Structure Data
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.
Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics
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.
