Nano to Meso and Back Again: Capturing and Exploiting Dynamic Heterogeneities in Biological Membranes via Large Scale Simulations
纳米到介观再返回:通过大规模模拟捕获和利用生物膜中的动态异质性
基本信息
- 批准号:BB/R00126X/1
- 负责人:
- 金额:$ 44.93万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Membranes are of fundamental importance to biology: they form the 'surrounding walls' of all cells, and control the flow of materials and information into and out of cells. The proteins of membranes are embedded in a lipid bilayer, which is an oil-like film separating the cellular contents from its watery external environment. These membrane proteins are responsible for many key biological functions, including communication between cells, and consequently are targets for many drugs, including some antibiotics. However, membranes are more than a simple 'sum of their parts'. Rather, they are complex and dynamic assemblies of proteins and lipids, and their biological functions are emergent properties of the membrane system as a whole. The overall aim of this proposal is to develop methods to understand how the various components of membranes are dynamically organized so as to carry out their biological functions.Computer simulations of the interacting molecules (proteins and lipids) which make up cell membranes may be used to study their dynamic behaviour and organization. Simulation studies to date have been limited to the very small (nano)scale, and have focused on e.g. the interactions of single membrane proteins with immediately neighbouring lipid molecules. However, larger scale simulations are needed to address (sub)cellular scales of the dynamic organization of cell membranes. These larger scale simulations will enable direct comparison of predictions emerging from simulations with experimental observations. We will develop larger scale simulations using 'meso' scale models which can be built using the outcomes of smaller scale models and simulations which have already been successfully employed to study isolated membrane proteins.We will use advanced computer simulations, benefiting from UK investment in national supercomputing facilities, to:1. Develop biologically realistic models of dynamic spatial heterogeneities in cell membranes; and2. Link smaller scale (coarse-grained) and larger scale (meso) models with experimental data in an integrated approach allowing us to bridge between structural and cellular studies of membranes. Thus, the overall outcome of these studies will be a powerful new computer simulation method for biological membranes, which will have applications relevant to the pharmaceutical and biotechnology sectors.
膜对生物学至关重要:它们构成了所有细胞的“周围壁”,并控制着物质和信息进出细胞的流动。膜上的蛋白质嵌在脂质双分子层中,脂质双分子层是一种类似油的膜,将细胞内容物与其水的外部环境分开。这些膜蛋白负责许多关键的生物功能,包括细胞之间的通讯,因此是许多药物的靶标,包括一些抗生素。然而,膜不仅仅是简单的“各部分的总和”。相反,它们是蛋白质和脂质的复杂和动态的组合,它们的生物学功能是膜系统作为一个整体的紧急特性。本提案的总体目标是发展方法来了解膜的各种成分是如何动态组织的,以执行其生物学功能。组成细胞膜的相互作用分子(蛋白质和脂质)的计算机模拟可以用来研究它们的动态行为和组织。迄今为止的模拟研究仅限于非常小的(纳米)尺度,并且集中在例如单个膜蛋白与邻近脂质分子的相互作用上。然而,需要更大规模的模拟来解决(亚)细胞尺度的细胞膜的动态组织。这些更大规模的模拟将使模拟预测与实验观测结果进行直接比较成为可能。我们将使用“中尺度”模型开发更大规模的模拟,这些模型可以使用已经成功用于研究分离膜蛋白的小尺度模型和模拟的结果来构建。我们将使用先进的计算机模拟,受益于英国对国家超级计算设施的投资,以:发展细胞膜动态空间异质性的生物现实模型;每天在家。将小尺度(粗粒度)和大尺度(中观)模型与实验数据结合起来,使我们能够在膜的结构和细胞研究之间架起桥梁。因此,这些研究的总体结果将是一种强大的新的生物膜计算机模拟方法,这将在制药和生物技术领域有相关的应用。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The energetics and ion coupling of cholesterol transport through Patched1.
- DOI:10.1126/sciadv.adh1609
- 发表时间:2023-08-25
- 期刊:
- 影响因子:13.6
- 作者:Ansell, T. Bertie;Corey, Robin A.;Viti, Lucrezia Vittoria;Kinnebrew, Maia;Rohatgi, Rajat;Siebold, Christian;Sansom, Mark S. P.
- 通讯作者:Sansom, Mark S. P.
Membrane Interactions of a-Synuclein Revealed by Multiscale Molecular Dynamics Simulations, Markov State Models, and NMR
多尺度分子动力学模拟、马尔可夫态模型和 NMR 揭示了 a-突触核蛋白的膜相互作用
- DOI:10.1101/2020.06.18.156216
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Amos S
- 通讯作者:Amos S
Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix.
- DOI:10.1021/acsnano.0c05960
- 发表时间:2020-12-22
- 期刊:
- 影响因子:17.1
- 作者:Belessiotis-Richards A;Higgins SG;Sansom MSP;Alexander-Katz A;Stevens MM
- 通讯作者:Stevens MM
The Energetics and Ion Coupling of Cholesterol Transport Through Patched1
- DOI:10.1101/2023.02.14.528445
- 发表时间:2023-02
- 期刊:
- 影响因子:0
- 作者:T. Ansell;R. Corey;Lucrezia Vittoria Viti;M. Kinnebrew;R. Rohatgi;C. Siebold;M. Sansom
- 通讯作者:T. Ansell;R. Corey;Lucrezia Vittoria Viti;M. Kinnebrew;R. Rohatgi;C. Siebold;M. Sansom
Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.
- DOI:10.1021/acs.jctc.1c00547
- 发表时间:2021-10-12
- 期刊:
- 影响因子:5.5
- 作者:Ansell TB;Curran L;Horrell MR;Pipatpolkai T;Letham SC;Song W;Siebold C;Stansfeld PJ;Sansom MSP;Corey RA
- 通讯作者:Corey RA
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Mark Sansom其他文献
Simulation Studies of Transport of Hydrophobic Compounds through Outer Membrane Proteins of Gram Negative Bacteria
- DOI:
10.1016/j.bpj.2011.11.2358 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Pragya Chohan;Syma Khalid;Mark Sansom - 通讯作者:
Mark Sansom
Invited Speaker CFTR: Molecular Models of the Anion Conduction Path
- DOI:
10.1016/j.bpj.2010.12.2175 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
David C. Dawson;Mark Sansom - 通讯作者:
Mark Sansom
Anion Translocation in a Brush-Like Nanopore: Simulations of the Outer Membrnae Protein OprP
- DOI:
10.1016/j.bpj.2009.12.292 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Prapasiri Pongprayoon;Oliver Beckstein;Chze Ling Wee;Mark Sansom - 通讯作者:
Mark Sansom
CFTR: Differential Reactivity, State-dependent Accessibility And Blocker Occlusion Of Cysteines Substituted For Adjacent Residues In TM6
- DOI:
10.1016/j.bpj.2008.12.2412 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Yohei Norimatsu;Anthony Ivetac;Christopher Alexander;Xuehong Liu;Mark Sansom;David C. Dawson - 通讯作者:
David C. Dawson
Homology Modeling and Molecular Dynamics Simulation Predict Side-Chain Orientations and Conformational Changes in the Pore of the CFTR Chloride Channel
- DOI:
10.1016/j.bpj.2009.12.1751 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Christopher Alexander;Anthony Ivetac;Yohei Norimatsu;Mark Sansom;David C. Dawson - 通讯作者:
David C. Dawson
Mark Sansom的其他文献
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{{ truncateString('Mark Sansom', 18)}}的其他基金
Hydrophobic Gating in Membrane Nanopores: Water at the Nanoscale
膜纳米孔中的疏水门控:纳米尺度的水
- 批准号:
EP/R004722/1 - 财政年份:2017
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
Crowding and Complexity: Simulation Studies of Biologically Realistic Membrane Models
拥挤和复杂性:生物真实膜模型的模拟研究
- 批准号:
BB/L002558/1 - 财政年份:2014
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
CCP-BioSim: Biomolecular simulation at the life sciences interface
CCP-BioSim:生命科学界面的生物分子模拟
- 批准号:
EP/J010421/1 - 财政年份:2012
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
MemProtMD: A resource for membrane proteins
MemProtMD:膜蛋白资源
- 批准号:
BB/I019855/1 - 财政年份:2011
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
OMSys: Towards a systems model of a bacterial outer membrane
OMSys:建立细菌外膜的系统模型
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BB/H000267/1 - 财政年份:2009
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
Simulations for Synthetic Biology: Mapping Biological Switches
合成生物学模拟:绘制生物开关
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EP/G042659/1 - 财政年份:2009
- 资助金额:
$ 44.93万 - 项目类别:
Research Grant
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