Abstract
Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.
Highlights
To answer these questions, a well-defined complex structure of the TRIM24 protein and its target modification histone is essential
Our analysis shows that correlation networks are significantly different between wild type structure (WT) and modification
Molecular dynamics simulations and inter-residue correlation network analyses were conducted on the complexes of TRIM24 and histone modifications
Summary
A well-defined complex structure of the TRIM24 protein and its target modification histone is essential. Residues A1-K9 of histone are located at the hydrophobic cleft of the PHD finger. In this study we utilized well-established all-atom molecular dynamics (MD) simulations in explicit solvent to study the dynamics features of the TRIM24/Histone complex. We constructed residue-level fluctuation correlation networks for the wild type and modified TRIM24-Histone complexes.
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