Information Fusion in Biomolecular Structure and Motion Determination
生物分子结构和运动测定中的信息融合
基本信息
- 批准号:8889276
- 负责人:
- 金额:$ 36.44万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-10 至 2019-04-30
- 项目状态:已结题
- 来源:
- 关键词:AlgorithmsAlzheimer&aposs DiseaseApplications GrantsArchitectureBiologicalCalculiCollaborationsComplexComputer softwareCrystallographyDataData SetDatabasesDockingElectron MicroscopyFamilyGated Ion ChannelGlutamate ReceptorGoalsGrowthHealthImageIndividualInformation SciencesInformation TheoryLengthLettersLigandsLinkMacromolecular ComplexesMainstreamingMeasurementMethodologyMethodsModalityModelingMolecular ConformationMolecular StructureMotionNatureNucleosomesPhaseProbability TheoryProceduresProteinsResistanceResolutionRoentgen RaysSamplingSignal TransductionSourceStrokeStructureStudentsSystemTechniquesTestingValidationWorkbasebiophysical techniquescancer typecase-by-case basiscell transformationchromatin remodelingcomputer codedata integrationdensityexperienceflexibilityimprovedinsightinterestmacromolecular assemblymathematical methodsmathematical modelnovelprogramstheoriestoolweb page
项目摘要
DESCRIPTION (provided by applicant): Due to their inherently complex nature, the architecture and motions of large macromolecular assemblies composed of rigid constituents are typically dissected using multiple techniques. While often combined on a case-by-case basis, the lack of theoretical tools to optimally integrate information from different sources is a
major barrier to generating a more complete/accurate understanding of important assemblies. Herein are proposed new information fusion algorithms for these assemblies, and their associated functional motions. This extends classical information science to the case of data on the Lie group of rigid-body motions. Utilizing data from electron microscopy (EM) and small-angle X-ray scattering (SAXS) measurements, these fusion algorithms will be applied to two large biomolecular assemblies: (1) the ionotropic glutamate receptor (iGluR), and (2) the Chd1-nucleosome complex. The specific aims are as follows:
SA1: To develop new information-theoretic methods based on Euclidean-group calculus and probability theory to improve fitting of macromolecular structures into EM densities and SAXS envelopes, and to perform information fusion of compatible biophysical information from different modalities to produce greater understanding than when methods are taken individually.
SA2: To apply mathematically optimized models of iGluR quaternary structure to uncover physiologically relevant conformational changes inaccessible to individual experimental methods.
SA3: To develop and apply new mathematical models of flexibility and ensemble dynamics of the nucleosome alone and in complex with the Chd1 chromatin remodeler using EM and SAXS, leading to a better understanding of the structure-motion-function relationship. The results will validate novel algorithms for fusing information from different experimental approaches to determine conformational changes in macromolecular complexes. If successful, these algorithms will provide new mechanistic insights into the iGluR family of ligand-gated ion channels, implicated in stroke and Alzheimer's disease, and the Chd1 remodeler, which has been linked to several types of cancer.
描述(由申请人提供):由于其固有的复杂性质,通常使用多种技术来剖析由刚性成分组成的大分子组装体的结构和运动。虽然经常在个案基础上进行组合,但缺乏理论工具来优化整合来自不同来源的信息是一个挑战。
这是对重要组件产生更完整/准确理解的主要障碍。在此提出了新的信息融合算法,这些组件,和他们相关的功能运动。这将经典信息科学扩展到刚体运动李群数据的情况。利用电子显微镜(EM)和小角X射线散射(SAXS)测量的数据,这些融合算法将被应用于两个大的生物分子组装:(1)离子型谷氨酸受体(iGluR),和(2)Chd 1-核小体复合物。具体目标如下:
SA1:开发基于欧几里得群演算和概率论的新的信息理论方法,以改善大分子结构与EM密度和SAXS包络的拟合,并对来自不同模态的兼容生物物理信息进行信息融合,以产生比单独使用方法更好的理解。
SA2:应用iGluR四级结构的数学优化模型,以揭示个体实验方法无法获得的生理相关构象变化。
SA3:开发和应用新的数学模型的灵活性和合奏动力学的核小体单独和复杂的Chd 1染色质重塑使用EM和SAXS,导致更好地理解的结构-运动-功能的关系。结果将验证新的算法融合信息从不同的实验方法,以确定在大分子复合物的构象变化。如果成功,这些算法将为iGluR家族的配体门控离子通道提供新的机制见解,涉及中风和阿尔茨海默病,以及与几种类型癌症有关的Chd 1重塑。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Gregory Chirikjian其他文献
Gregory Chirikjian的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Gregory Chirikjian', 18)}}的其他基金
Information Fusion in Biomolecular Structure and Motion Determination
生物分子结构和运动测定中的信息融合
- 批准号:
8825691 - 财政年份:2014
- 资助金额:
$ 36.44万 - 项目类别:
Information Fusion in Biomolecular Structure and Motion Determination
生物分子结构和运动测定中的信息融合
- 批准号:
9059739 - 财政年份:2014
- 资助金额:
$ 36.44万 - 项目类别:
Information Fusion in Biomolecular Structure and Motion Determination
生物分子结构和运动测定中的信息融合
- 批准号:
9261553 - 财政年份:2014
- 资助金额:
$ 36.44万 - 项目类别:
Group-Theoretic Methods in Protein Structure Determina-n
蛋白质结构测定中的群论方法
- 批准号:
7845819 - 财政年份:2009
- 资助金额:
$ 36.44万 - 项目类别:
Group-Theoretic Methods in Protein Structure Determina-n
蛋白质结构测定中的群论方法
- 批准号:
7404474 - 财政年份:2005
- 资助金额:
$ 36.44万 - 项目类别:
Group-Theoretic Methods in Protein Structure Determina-n
蛋白质结构测定中的群论方法
- 批准号:
7214174 - 财政年份:2005
- 资助金额:
$ 36.44万 - 项目类别:
Group-Theoretic Methods in Protein Structure Determina-n
蛋白质结构测定中的群论方法
- 批准号:
7035801 - 财政年份:2005
- 资助金额:
$ 36.44万 - 项目类别:
Group-Theoretic Methods in Protein Structure Determina-n
蛋白质结构测定中的群论方法
- 批准号:
6985636 - 财政年份:2005
- 资助金额:
$ 36.44万 - 项目类别: