TMB

TMB provides a library of all-atom molecular dynamics simulations of nucleosomes (145–147 base pairs of DNA wrapped ~1.7 turns around a histone octamer) for comparative analysis of sequence-dependent nucleosome structure and dynamics.

Key Features:

• Simulation ensemble: Meta-analysis of over 20 microseconds of all-atom molecular dynamics representing 518 distinct nucleosome realizations.
• Simulation outputs: Dewatered trajectories, root-mean-square deviation (RMSD) metrics, and DNA helical parameter datasets are provided for each simulation.
• Nucleosomal conformation insights: Demonstrates that nucleosomal DNA adopts a left-handed superhelix while base- and base-pair-level conformational ranges are not more restricted than in free solution.
• Sequence-dependent effects: Detects DNA sequence influences on nucleosome structure and dynamics, including DNA kinking and mispositioning of sequences such as the 601 super strong positioning sequence, observable in simulations as short as 10 nanoseconds.
• Comparative analysis support: Provides a robust dataset to enable comparative simulation studies of nucleosome behavior and interactions with proteins and drugs.

Scientific Applications:

• Comparative nucleosome studies: Benchmarking and comparative analysis of nucleosome conformations across sequence variants and simulation conditions.
• Sequence effect characterization: Investigation of sequence-specific phenomena such as DNA kinking and positioning, including behavior of the 601 super strong positioning sequence.
• Interaction studies: Assessing how nucleosome structure and dynamics influence and respond to interactions with proteins and drugs.
• Reference dataset for simulations: Serving as a reference ensemble for interpreting or designing on-demand nucleosome simulations.

Methodology:

All-atom molecular dynamics simulations totaling over 20 microseconds across 518 nucleosome realizations with analysis of dewatered trajectories, RMSD calculations, extraction of DNA helical parameters, and meta-analysis.