Modeling and Interacting with the Visible Molecular Cell

可见分子细胞建模并与之交互

基本信息

批准号：
10689043
负责人：
DAVID S GOODSELL
金额：
$ 45.45万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10689043
关键词：
3-Dimensional Actins Address Articulation Automobile Driving Bacterial Genome Bacterial Model Biological Cell model Cells Collaborations Communities Complex Computational Biology Computer software Data Data Set Databases Dendritic Spines Development Education and Outreach Electrons Generations Genome Glass Goals Heterogeneity Image Intuition Knowledge Laboratories Methods Mitochondria Modeling Molecular Molecular Structure Mycoplasma Organelles Organism Property Proteins Proteomics Research Personnel Resolution Roentgen Rays Structural Models Structure Structure of beta Cell of islet System Technology Testing Time Tomogram Validation Visualization Work biological systems computer infrastructure data integration experience in silico interest method development mitochondrial genome model building models and simulation novel prototype simulation structural biology three-dimensional modeling tomography tool usability user-friendly

项目摘要

PROJECT SUMMARY Integrative structural modeling of entire cells is a grand challenge actively being addressed by the structural biology community. The complexity and heterogeneity of structural models of entire cells poses several distinct challenges that are testing the current limits of technology and understanding. To tackle these challenges, we are developing the CellPACK Suite, a functional prototype of an entire integrative structural modeling pipeline. This pipeline allows users to gather and curate data from proteomics and structural databases, and to integrate this data into representative structural models that can be used for hypothesis generation and in-silico testing. Our goal is to continue to develop, enhance, and harden this software, and to continue the application and validation of mesoscale modeling methods to biomedically relevant problems. The development will be driven by multiple collaborations with experimental and computational biologists with a focus on using mesoscale models to interpret and validate tomographic data, and on functional modeling of nucleoid structure in the context of entire bacterial cells and mitochondria. Throughout this work, we will work in the classic integrative structural biology mode, building models to interpret and reconcile 3D experimental tomographic data, and using models to infer the detailed molecular structure within tomographic data sets of limited resolution. We plan to expand and harden our growing toolbox for structural integrative modeling by developing new methods to incorporate specific interactions between molecules and working to increase the range of systems that are achievable. We are also committed to creating user-friendly and targeted tools for the wider biological community and have created prototypes of software that allow facile model creation and hypothesis-testing by non-expert users. My laboratory brings 30 years of experience in gathering and integrating diverse biological data to depict the cellular mesoscale, and in the past 10 years, development of quantitative approaches to modeling the cellular mesoscale as computational infrastructure has progressed to the level where this is possible. Throughout this work, we have taken a practical, but exploratory, approach to methods development, building novel tools to address the underlying questions posed by our experimental collaborators, and then hardening the most effective tools to make them accessible to the larger computational biology community. We intend to create an accessible and effective toolbox for integrative modeling at the cellular mesoscale, driven by collaborative applications that span from atoms to cells.

项目摘要整个细胞的整合结构建模是一个巨大的挑战生物学社区。整个细胞结构模型的复杂性和异质性构成了几个正在测试技术和理解的局限性的独特挑战。解决这些挑战，我们正在开发CellPack Suite，这是整个集成结构的功能原型建模管道。该管道使用户可以从蛋白质组学和结构上收集和策划数据数据库，并将这些数据集成到可以用于假设的代表性结构模型中产生和内部测试。我们的目标是继续开发，增强和硬化该软件，以及继续在生物医学相关问题上应用和验证中尺度建模方法。该开发将由与实验和计算生物学家与专注于使用中尺度模型来解释和验证层析成像数据以及功能建模在整个细菌细胞和线粒体的背景下的核苷结构。在整个工作中，我们将在经典的集成结构生物学模式下工作，建立解释和调和3D的模型实验断层扫描数据，并使用模型推断层析成像内的详细分子结构分辨率有限的数据集。我们计划扩展和加强我们成长的工具箱以进行结构集成通过开发新方法来建模，以结合分子之间的特定相互作用并致力于增加可实现的系统范围。我们还致力于创建用户友好的针对更广泛的生物界的有针对性工具，并创建了允许便捷的软件原型非专家用户的模型创建和假设测试。我的实验室带来了30年的经验收集和整合潜水员的生物学数据以描绘细胞中尺度，并且在过去的10年中开发定量方法来建模细胞中尺度作为计算和基础设施已经发展到可能的水平。通过这项工作，我们做了一个实用的，但是探索性，方法开发方法，建立新的工具来解决基本问题由我们的实验合作者提出，然后硬化最有效的工具以使其可访问到更大的计算生物学社区。我们打算为在蜂窝中尺度上进行集成建模，这是由从原子到原子到的协作应用驱动的细胞。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lattice Models of Bacterial Nucleoids.

DOI：
10.1021/acs.jpcb.7b11770
发表时间：
2018-05-31
期刊：
The journal of physical chemistry. B
影响因子：
0
作者：
Goodsell DS;Autin L;Olson AJ
通讯作者：
Olson AJ

Multiplayer virtual reality for understanding biomolecular structures.

用于理解生物分子结构的多人虚拟现实。

DOI：
10.1016/j.tibs.2023.07.001
发表时间：
2023
期刊：
Trends in biochemical sciences
影响因子：
13.8
作者：
Autin,Ludovic;Gardner,Adam;Olson,Arthur
通讯作者：
Olson,Arthur

Mesoscope: A Web-based Tool for Mesoscale Data Integration and Curation.

DOI：
10.2312/molva.20201098
发表时间：
2020-05-01
期刊：
MolVa : Workshop on Molecular Graphics and Visual Analysis of Molecular Data 2020
影响因子：
0
作者：
Autin, L;Maritan, M;Goodsell, D S
通讯作者：
Goodsell, D S

Modeling in the Time of COVID-19: Statistical and Rule-based Mesoscale Models.

DOI：
10.1109/tvcg.2020.3030415
发表时间：
2021-03
期刊：
IEEE transactions on visualization and computer graphics
影响因子：
5.2
作者：
Nguyen N;Strnad O;Klein T;Luo D;Alharbi R;Wonka P;Maritan M;Mindek P;Autin L;Goodsell DS;Viola I
通讯作者：
Viola I

Integrative modeling of JCVI-Syn3A nucleoids with a modular approach.