Theory and Modeling of Biomolecules and their Interactions
生物分子及其相互作用的理论和建模
基本信息
- 批准号:10094219
- 负责人:
- 金额:$ 83.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsActin-Binding ProteinAddressAreaBig DataBiologicalBiomedical ResearchCREBBP geneChemicalsCollaborationsCommunitiesComplexComputer SimulationComputer softwareComputing MethodologiesDevelopmentDockingEnvironmentEnzymesEquilibriumEvolutionFibroblast Growth FactorFlavinsFree EnergyGTP-Binding ProteinsGenetic TranscriptionGoalsHRX proteinInterleukinsLigand BindingLigandsMED25 geneMalignant NeoplasmsMediatingMediationMeninMethodologyMethodsMixed Function OxygenasesModelingMolecularNucleic AcidsOncogenicPharmaceutical PreparationsPharmacologic SubstancePhosphotransferasesPlayProcessProteinsProtocols documentationResearchRoleSignal TransductionStatistical MechanicsStatistical MethodsStructureTechnologyTestingThermodynamicsTranscriptional ActivationWorkbasecancer therapydesigninhibitor/antagonistinnovationinsightmodels and simulationmolecular dynamicsnovelprotein protein interactionprotonationreceptorsensorsimulationsmall moleculesoftware developmentsoftware infrastructuretheoriestool
项目摘要
Project Summary/Abstract
The establishment of tools and methods from statistical mechanics and computer simulation technology to
enable the exploration of biological molecules and their interactions plays a central role in discovery within
biomedical research. This proposal represents a request for support of our ongoing efforts in this area and
includes objectives to address challenges in the theory and modeling associated with these problems, as well
as strategically chosen collaborations that will help elucidate important biomedical questions and provide crucial
tests of the approaches we develop. Our proposed development efforts include the exploration of receptor-ligand
interactions and the thermodynamics of ligand binding to biological receptors through the continued development
and application of novel methods of free energy simulations to ligand binding thermodynamics, docking and
receptor-ligand interaction modeling. The continued refinement, hardening and application of theoretical and
computational methods of constant pH molecular dynamics to integrate the critical aspects of pH and protonation
state changes in protein and nucleic acid receptors and their ligands in molecular simulations and modeling
represents another challenge we will continue to address with the proposed work. Finally, software
infrastructure, specifically the CHARMM macromolecular simulation package, provides the framework for
advancing our methodological approaches and enabling the broader community to explore biomedically
motivated questions via its wide usage and distribution. A component of our proposed efforts will be to continue
the innovative implementation of methods and simulation approaches into this community standard software
package. We will balance and drive our development efforts in the areas of free energy simulations, ligand –
receptor docking and pH-mediated structure-function processes, important to a deeper mechanistic
understanding of biomedically directed questions, through strategic collaborations with experimental colleagues
in the areas of: transcriptional activation based on small amphipathic molecules targeting co-activators from the
CREB binding protein (KIX) and the AciD domain of Med25; key cancer targets such as menin-MLL protein-
protein interaction inhibition; inhibitors of acyl protein thioesterases, targeted in anti-cancer therapies for
oncogenic HRas; enzyme redesign and substrate scope expansion to better understand the evolution of function
of a novel Flavin-dependent hydroxylase in exploiting complex chemical transformations important in the
development of pharmaceuticals; pH-regulated sensors in kinase signaling associated with the G-protein from
the tetrameric Gai protein; the pH-modulated switch for myristoylated histactophilin, the actin binding protein that
is structurally homologous with interleukin-1b and fibroblast growth factor. Finally, we will engage experts in the
development of big data applications of molecular simulations and the design and execution of robust user APIs
to work with us toward advancing objectives in software development for large multi-scale simulations of cellular
environments and automated workflows, through CHARMM-GUI, for sophisticated simulation protocols.
项目总结/文摘
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 }}
CHARLES L BROOKS其他文献
CHARLES L BROOKS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('CHARLES L BROOKS', 18)}}的其他基金
Theory and Modeling of Biomolecules and their Interactions - Equipment Supplement
生物分子及其相互作用的理论和建模 - 设备补充
- 批准号:
9894101 - 财政年份:2019
- 资助金额:
$ 83.16万 - 项目类别:
Theory and Modeling of Biomolecules and their Interactions - Equipment Supplement
生物分子及其相互作用的理论和建模 - 设备补充
- 批准号:
10580491 - 财政年份:2019
- 资助金额:
$ 83.16万 - 项目类别:
Theory and Modeling of Biomolecules and their Interactions
生物分子及其相互作用的理论和建模
- 批准号:
10554419 - 财政年份:2019
- 资助金额:
$ 83.16万 - 项目类别:
Theory and Modeling of Biomolecules and their Interactions
生物分子及其相互作用的理论和建模
- 批准号:
10333335 - 财政年份:2019
- 资助金额:
$ 83.16万 - 项目类别:
Acid-mediated processes in nucleic acids and proteins
核酸和蛋白质中酸介导的过程
- 批准号:
8854117 - 财政年份:2014
- 资助金额:
$ 83.16万 - 项目类别:
Acid-mediated processes in nucleic acids and proteins
核酸和蛋白质中酸介导的过程
- 批准号:
8691310 - 财政年份:2014
- 资助金额:
$ 83.16万 - 项目类别:
Acid-mediated processes in nucleic acids and proteins
核酸和蛋白质中酸介导的过程
- 批准号:
9068970 - 财政年份:2014
- 资助金额:
$ 83.16万 - 项目类别:
Acid-mediated processes in nucleic acids and proteins
核酸和蛋白质中酸介导的过程
- 批准号:
9294086 - 财政年份:2014
- 资助金额:
$ 83.16万 - 项目类别:
CORE 2006-2011: COMPUTATIONAL IMPLEMENTATION OF A TIME CORRELATION FUNCTION THE
CORE 2006-2011:时间相关函数的计算实现
- 批准号:
8364273 - 财政年份:2011
- 资助金额:
$ 83.16万 - 项目类别:
相似海外基金
Impact of actin binding protein Coronin 1C in the pathogenesis of Parkinson's disease
肌动蛋白结合蛋白 Coronin 1C 在帕金森病发病机制中的影响
- 批准号:
10392204 - 财政年份:2022
- 资助金额:
$ 83.16万 - 项目类别:
Impact of actin binding protein Coronin 1C in the pathogenesis of Parkinson's disease
肌动蛋白结合蛋白 Coronin 1C 在帕金森病发病机制中的影响
- 批准号:
10577415 - 财政年份:2022
- 资助金额:
$ 83.16万 - 项目类别:
Functional Role of Actin-binding Protein Moesin in Renal Tubules.
肌动蛋白结合蛋白 Moesin 在肾小管中的功能作用。
- 批准号:
18K06643 - 财政年份:2018
- 资助金额:
$ 83.16万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An actin-binding protein villin in Marchantia polymorpha
地钱中的肌动蛋白结合蛋白绒毛蛋白
- 批准号:
18K06287 - 财政年份:2018
- 资助金额:
$ 83.16万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Analysis of the role of actin-binding protein in tooth germ formation
肌动蛋白结合蛋白在牙胚形成中的作用分析
- 批准号:
17K17311 - 财政年份:2017
- 资助金额:
$ 83.16万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Interaction between NMDA receptor subunits and drebrin, an actin binding protein
NMDA 受体亚基与肌动蛋白结合蛋白 drebrin 之间的相互作用
- 批准号:
16K18376 - 财政年份:2016
- 资助金额:
$ 83.16万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
The F-actin binding protein TRIOBP-1 regulates hERG K+ channels
F-肌动蛋白结合蛋白 TRIOBP-1 调节 hERG K 通道
- 批准号:
9051240 - 财政年份:2016
- 资助金额:
$ 83.16万 - 项目类别:
Signal transduction of the actin-binding protein cortactin in bacterial pathogenesis
肌动蛋白结合蛋白 cortactin 在细菌发病机制中的信号转导
- 批准号:
289286761 - 财政年份:2016
- 资助金额:
$ 83.16万 - 项目类别:
Research Grants
The role of PPP1r18, an actin binding protein, in osteoclastic bone resorption
肌动蛋白结合蛋白 PPP1r18 在破骨细胞骨吸收中的作用
- 批准号:
16K20423 - 财政年份:2016
- 资助金额:
$ 83.16万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Control of matrix remodeling through an actin binding protein
通过肌动蛋白结合蛋白控制基质重塑
- 批准号:
354556 - 财政年份:2016
- 资助金额:
$ 83.16万 - 项目类别:
Operating Grants