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Made available in DSpace on 2021-06-25T10:45:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-19 Significant efforts have been recently made to obtain the three-dimensional (3D) structure of the genome with the goal of understanding how structures may affect gene regulation and expression. Chromosome conformational capture techniques such as Hi-C, have been key in uncovering the quantitative information needed to determine chromatin organization. Complementing these experimental tools, co-polymers theoretical methods are necessary to determine the ensemble of three-dimensional structures associated to the experimental data provided by Hi-C maps. Going beyond just structural information, these theoretical advances also start to provide an understanding of the underlying mechanisms governing genome assembly and function. Recent theoretical work, however, has been focused on single chromosome structures, missing the fact that, in the full nucleus, interactions between chromosomes play a central role in their organization. To overcome this limitation, MiChroM (Minimal Chromatin Model) has been modified to become capable of performing these multi-chromosome simulations. It has been upgraded into a fast and scalable software version, which is able to perform chromosome simulations using GPUs via OpenMM Python API, called Open-MiChroM. To validate the efficiency of this new version, analyses for GM12878 individual autosomes were performed and compared to earlier studies. This validation was followed by multi-chain simulations including the four largest human chromosomes (C1-C4). These simulations demonstrated the full power of this new approach. Comparison to Hi-C data shows that these multiple chromosome interactions are essential for a more accurate agreement with experimental results. Without any changes to the original MiChroM potential, it is now possible to predict experimentally observed inter-chromosome contacts. This scalability of Open-MiChroM allow for more audacious investigations, looking at interactions of multiple chains as well as moving towards higher resolution chromosomes models. Center for Theoretical Biological Physics Rice University ICTP South American Institute for Fundamental Research Instituto de Física Teórica Instituto de Biociências Letras e Ciências Exatas UNESP - Univ. Estadual Paulista Departamento de Física São José do Rio Preto Chemical Engineering Department Military Institute of Engineering Instituto de Biociências Letras e Ciências Exatas UNESP - Univ. Estadual Paulista Departamento de Física São José do Rio Preto

Made available in DSpace on 2018-11-12T17:27:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2018. Added 1 bitstream(s) on 2021-07-14T17:51:22Z : No. of bitstreams: 1 S1806-11172018000400407.pdf: 16053464 bytes, checksum: 05cd6507810278fc2f0b49b98b824b8e (MD5) Resumo Este trabalho tem como objetivo introduzir estudantes de física e áreas afins ao problema de enovelamento de proteína. A proteína é uma macromolécula biológica de grande importância para os seres vivos. Entender como esta macromolécula encontra uma configuração tridimensional e funcional, tomando como a priori a informação presente em uma sequência linear de diferentes aminoácidos, é uma questão relevante e envolve pesquisadores de diversas áreas do conhecimento. Neste trabalho, é apresentada uma introdução sobre a importância das proteínas e suas principais características, além de mostrar um breve histórico do estudo de enovelamento de proteínas e como esses trabalhos convergem na construção da teoria de Superfície de Energia. São descritos alguns modelos teóricos e computacionais, desde as primeiras abordagens em modelos analíticos até a construção de modelos baseados em estruturas para simulações. Também são apresentados e discutidos alguns resultados esperados em cada modelo utilizado. Abstract This work aims to introduce students of physics and related areas to the problem of protein folding. Proteins are biological macromolecules of great importance to living things. The understanding of how this macromolecule finds a three-dimensional and functional structure, using the information present in a linear sequence of different amino acids, is a relevant question which involves researchers from different areas of knowledge. This work discusses the importance and the main properties of proteins and presents a brief history of protein folding studies and how these works converge to the Energy Landscape theory. There are described some theoretical and computational models from analytical approaches to the development of the Structure-Based Models for simulations. Here it is also presented and discussed some expected results for each used model. Centro Nacional de Pesquisa em Energia e Materiais Laboratório Nacional de Ciência e Tecnologia do Bioetanol Universidade Estadual Paulista Instituto de Biociências Departamento de Física Rice University Center for Theoretical Biological Physics Universidade Federal do Triângulo Mineiro Instituto de Ciências Exatas Departamento de Física Universidade Estadual Paulista Instituto de Biociências Departamento de Física