Combining Machine Learning, Molecular Dynamics and Membrane Biophysics to identify new therapeutics for the treatment of Tuberculosis
结合机器学习、分子动力学和膜生物物理学来确定治疗结核病的新疗法
基本信息
- 批准号:2277910
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2019
- 资助国家:英国
- 起止时间:2019 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Tuberculosis (TB) is currently one of the world's leading causes of mortality with 10 million new cases reported in 2017 alone and 1.3 million deaths (Global Tuberculosis Report 2018 WHO), a further complicating factor is the evolution of multi-drug and totally drug resistant strains. There is an urgent need to develop effective new therapeutic agents to target TB and critical in this process is the identification of a suitable protein to target. MmpL3 is a transmembrane protein which is essential for the replication and viability of bacterial cells and therefore represents a suitable target. The recent determination of the structure of MmpL3 from M. smegmatis (Cell 2019; 176: 636-648) provides the starting point for developing new therapeutic strategies. Molecular Dynamics (MD) simulations will be utilised to construct a model of MmpL3 for M. tuberculosis (Mtb) facilitating investigation of drug-protein interactions, known inhibitors will be modelled at physiological conditions with the protein embedded in a realistic representation of the cell membrane. Validation of the computational model will be achieved through the investigation of the structure and mechanics of model membranes, in which Mtb MmpL3 is embedded, via X-ray diffraction and light microscopy. Identification of the binding modes of know inhibitors to Mtb MmpL3 and known drug resistant mutants will be used as input into Machine Learning (ML) to generate rules to search large compound libraries, in particular the Zinc database, to identify suitable compounds to screen. This project will provide the student with a broad range of skills, computational modelling, machine learning, protein expression and purification and experimental membrane biophysics.
结核病(TB)目前是世界上主要的死亡原因之一,仅2017年就报告了1000万新发病例,130万人死亡(2018年全球结核病报告WHO),另一个复杂因素是多药和完全耐药菌株的演变。迫切需要开发有效的新治疗剂来靶向TB,并且在该过程中关键的是鉴定合适的靶向蛋白质。MmpL 3是一种跨膜蛋白,其对于细菌细胞的复制和活力是必需的,因此代表了合适的靶标。MmpL 3的结构测定表明,MmpL 3的结构与MmpL 3的结构一致。smeglitazone(Cell 2019; 176:636-648)为开发新的治疗策略提供了起点。将利用分子动力学(MD)模拟来构建M的MmpL 3模型。结核分枝杆菌(Mtb)的抑制剂有助于研究药物-蛋白质相互作用,已知的抑制剂将在生理条件下建模,其中蛋白质嵌入细胞膜的真实表示中。计算模型的验证将通过研究模型膜的结构和力学来实现,其中Mtb MmpL 3被嵌入,通过X射线衍射和光学显微镜。已知抑制剂与Mtb MmpL 3和已知耐药突变体的结合模式的鉴定将被用作机器学习(ML)的输入,以生成搜索大型化合物文库(特别是锌数据库)的规则,从而鉴定合适的化合物以进行筛选。该项目将为学生提供广泛的技能,计算建模,机器学习,蛋白质表达和纯化以及实验膜生物物理学。
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 }}
其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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('', 18)}}的其他基金
An implantable biosensor microsystem for real-time measurement of circulating biomarkers
用于实时测量循环生物标志物的植入式生物传感器微系统
- 批准号:
2901954 - 财政年份:2028
- 资助金额:
-- - 项目类别:
Studentship
Exploiting the polysaccharide breakdown capacity of the human gut microbiome to develop environmentally sustainable dishwashing solutions
利用人类肠道微生物群的多糖分解能力来开发环境可持续的洗碗解决方案
- 批准号:
2896097 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
A Robot that Swims Through Granular Materials
可以在颗粒材料中游动的机器人
- 批准号:
2780268 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Likelihood and impact of severe space weather events on the resilience of nuclear power and safeguards monitoring.
严重空间天气事件对核电和保障监督的恢复力的可能性和影响。
- 批准号:
2908918 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Proton, alpha and gamma irradiation assisted stress corrosion cracking: understanding the fuel-stainless steel interface
质子、α 和 γ 辐照辅助应力腐蚀开裂:了解燃料-不锈钢界面
- 批准号:
2908693 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Field Assisted Sintering of Nuclear Fuel Simulants
核燃料模拟物的现场辅助烧结
- 批准号:
2908917 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Assessment of new fatigue capable titanium alloys for aerospace applications
评估用于航空航天应用的新型抗疲劳钛合金
- 批准号:
2879438 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
使用右旋糖酐-胶原蛋白水凝胶开发 3D 打印皮肤模型,以分析白细胞介素 17 抑制剂的细胞和表观遗传效应
- 批准号:
2890513 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
- 批准号:
2876993 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
相似国自然基金
Understanding structural evolution of galaxies with machine learning
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
相似海外基金
Screening of environmentally friendly quantum-nanocrystals for energy and bioimaging applications by combining experiment and theory with machine learning
通过将实验和理论与机器学习相结合,筛选用于能源和生物成像应用的环保量子纳米晶体
- 批准号:
23K20272 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
Combining Machine Learning Explanation Methods with Expectancy-Value Theory to Identify Tailored Interventions for Engineering Student Persistence
将机器学习解释方法与期望值理论相结合,确定针对工程学生坚持的定制干预措施
- 批准号:
2335725 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
Developing and Understanding Thermally Conductive Polymers by Combining Molecular Simulation, Machine Learning and Experiment
通过结合分子模拟、机器学习和实验来开发和理解导热聚合物
- 批准号:
2332270 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Development of a new EBSD analysis method combining dynamical scattering theory and machine learning
结合动态散射理论和机器学习开发新的 EBSD 分析方法
- 批准号:
23H01276 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
EAGER: SSMCDAT2023: Revealing Local Symmetry Breaking in Intermetallics: Combining Statistical Mechanics and Machine Learning in PDF Analysis
EAGER:SSMCDAT2023:揭示金属间化合物中的局部对称性破缺:在 PDF 分析中结合统计力学和机器学习
- 批准号:
2334261 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Standard Grant
Development of an efficient method combining quantum chemistry and machine learning to evolve PCR technology and gene mutation analysis
开发一种结合量子化学和机器学习的有效方法来发展 PCR 技术和基因突变分析
- 批准号:
22KJ2450 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for JSPS Fellows
Computer-assisted diagnosis of ear pathologies by combining digital otoscopy with complementary data using machine learning
通过使用机器学习将数字耳镜与补充数据相结合来计算机辅助诊断耳部病变
- 批准号:
10564534 - 财政年份:2023
- 资助金额:
-- - 项目类别:
CAREER: Combining Machine Learning and Physics-based Modeling Approaches for Accelerating Scientific Discovery
职业:结合机器学习和基于物理的建模方法来加速科学发现
- 批准号:
2239175 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Continuing Grant
Gibbs Energy Estimation of Amorphous Materials by Combining Microstructural Simulation and Machine Learning
结合微观结构模拟和机器学习的非晶材料吉布斯能量估计
- 批准号:
23KJ1094 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for JSPS Fellows