Associative Memory Hamiltonian Modeling on DNA, Nucleosomes, and Chromatin
| dc.contributor.advisor | Onuchic, Jose | |
| dc.creator | Lu, Weiqi | |
| dc.date.accessioned | 2024-01-24T21:36:36Z | |
| dc.date.available | 2024-01-24T21:36:36Z | |
| dc.date.created | 2023-12 | |
| dc.date.issued | 2023-09-21 | |
| dc.date.submitted | December 2023 | |
| dc.date.updated | 2024-01-24T21:36:36Z | |
| dc.description.abstract | Chromatin, the complex of DNA and proteins, plays a pivotal role in the regulation of gene expression and other cellular processes. Its dynamic organization and conformational plasticity are fundamental to the proper functioning of the genome. Understanding the three-dimensional structure and dynamics of chromatin at various scales is crucial for elucidating the molecular mechanisms underlying gene expression and other biological processes. However, the inherent complexity and multiscale nature of chromatin pose significant challenges for experimental and computational studies. In this thesis, we present the development and application of an Associative Memory Hamiltonian model, the Widely Editable Chromain Model (WEChroM) to gain insights into the structure and dynamics of chromatin fibers and nucleosomes. We begin by introducing the Associative Memory Hamiltonian approach, which leverages prior knowledge of experimentally determined structures to guide molecular dynamics simulations toward biologically relevant conformations. We detail the development of WEChroM for DNA and nucleosomes and demonstrate the model’s capability to capture conformational preferences and mechanical and thermodynamically properties. We investigate the bending and twisting persistence lengths, supercoiling behavior of DNA minicircles, and DNA-protein interactions within the context of nucleosomes. We further discuss the implementation of WEChroM on the OpenMM platform and provide a tutorial on the software. We then apply the WEChroM approach to investigate higher-order chromatin structures. We elucidate organization patterns in nucleosome arrays, explore the 30-nm fiber models, and assess the impact of uniform and non-uniform linker lengths.We discuss the functional implications of nucleosome array organization and compare our theoretical predictions with experimental data. Lastly, we discuss the significance, limitations, challenges, and future directions of the WEChroM approach. In summary, this thesis contributes to the field of computational genomics by providing insights into chromatin structure and dynamics through the development and application of the WEChroM model. Our findings have broad implications for understanding genome function, gene regulation, and the molecular mechanisms behind the phenomenon. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.citation | Lu, Weiqi. "Associative Memory Hamiltonian Modeling on DNA, Nucleosomes, and Chromatin." (2023). PhD diss., Rice University. https://hdl.handle.net/1911/115387 | |
| dc.identifier.uri | https://hdl.handle.net/1911/115387 | |
| dc.language.iso | eng | |
| dc.rights | Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | |
| dc.subject | chromatin | |
| dc.subject | nucleosome | |
| dc.subject | associative memory hamiltonian | |
| dc.title | Associative Memory Hamiltonian Modeling on DNA, Nucleosomes, and Chromatin | |
| dc.type | Thesis | |
| dc.type.material | Text | |
| thesis.degree.department | Physics and Astronomy | |
| thesis.degree.discipline | Natural Sciences | |
| thesis.degree.grantor | Rice University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy |
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