SYSTEMATIC COARSE-GRAINING OF LIPID BILAYERS WITH IMPLICIT SOLVENT

使用隐式溶剂对脂质双层进行系统粗粒化

• 批准号: 8171868
• 负责人: Markus Deserno
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171868
• 关键词: Accounting; Award; Biochemical; Biological; Biological Models; Cells; Cereals; Characteristics; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Coupling; Development; Endocytosis; Environment; Event; Freedom; Funding; Generic Drugs; Grant; Individuality; Institution; Learning; Length; Life; Link; Lipid Bilayers; Lipids; Liquid substance; Locomotion; Mediating; Membrane; Membrane Proteins; Modeling; Molecular; Nature; Organelles; Phase; Play; Property; Proteins; Research; Research Personnel; Resources; Role; Shapes; Signal Transduction; Solvents; Sorting - Cell Movement; Source; Structure; Supercomputing; System; Tail; Techniques; Time; United States National Institutes of Health; base; experience; interest; models and simulation; simulation; statistics

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lipid bilayers are one of the key structural components of all living cells. They compartmentalize and organize the cellular biochemical environment into organelles and play a key role in mediating controlled transport of substances and signals between spatially separated domains. Rather than merely solubilizing membrane proteins, as has long been believed, we now know that lipid bilayers actively participate in many of these cellular events, and this has generated a renewed interest in their biophysical and material characteristics. However, many of the events on which current research focuses -- vesiculation, sorting, endocytosis, sensing, locomotion, etc. -- occur on length- and associated time-scales which are significantly beyond the reach of atomistic molecular simulation techniques. Hence, much interest has been devoted to the development of coarse-grained models that reduce the number of required degrees of freedom and enable the systematic studies of phenomena which are largely independent of chemical detail [1]. Among them, models that eliminate the need for an embedding solvent hold the largest promise to finally bridge the gap to the organelle level [2], but they are still a very recent addition to the simulation toolbox and require further studies. The PI has recently developed a highly coarse-grained solvent-free lipid model [3] and successfully applied it to problems involving composition-curvature coupling [4] and curvature-mediated interactions [5]. While robustly representing large-scale membrane properties, it is not finely enough resolved to account for structural bilayer detail that matters for several aspects of lipid-protein interactions. In order to bridge the gap backwards to more detailed descriptions of lipids, the PI proposes to carefully reintroduce degrees of freedom and lipid species individuality, while at the same time keeping the embedding solvent implicit. The plan is to follow a structure-based coarse- (or fine-) graining technique which links existing atomistic and mesoscopic scales to the solvent free realm. Such an approach will in particular require significant computational power to obtain very good structural statistics on the finer levels of detail, thus necessitating the access to supercomputing facilities. The CPU time awarded within the framework of a DAC will both serve as an initial system startup and -- more importantly -- help to gain crucial experience and scaling information required to formulate a subsequent MRAC proposal. [1] M. Muller, K. Katsov, and M. Schick, "Biological and synthetic membranes: What can be learned from a coarse-grained description?", Phys. Rep. _434_, 113 (2006); M. Venturoli, M.M. Sperotto, M. Kranenburg, and B. Smit, "Mesoscopic models of biological membranes", Phys. Rep. _437_, 1 (2006). [2] G. Brannigan, L.C.L. Lin, and F.L.H Brown, "Implicit solvent simulation models for biomembranes", Eur. Biophys. J. _35_, 104 (2006). [3] I.R. Cooke, K. Kremer, and M. Deserno, "Tunable generic model for fluid bilayer membranes", Phys. Rev. E _72_, 011506 (2005); I.R. Cooke and M. Deserno, "Solvent-free model for self-assembling fluid bilayer membranes: Stabilization of the fluid phase based on broad attractive tail potentials", J. Chem. Phys. _123_, 224710 (2005). [4] I.R. Cooke and M. Deserno, "Coupling between lipid shape and membrane curvature", Biophys. J. _91_, 487 (2006). [5] B.J. Reynwar, G. Illya, V.A. Harmandaris, M.M. Muller, K. Kremer, and M. Deserno, "Aggregation and vesiculation of membrane proteins by curvature-mediated interactions", Nature _447_, 461-464 (2007).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 脂质双层是所有活细胞的关键结构成分之一。它们将细胞生化环境分为细胞器中，并在介导在空间分离域之间的受控转运和信号中起关键作用。长期以来，我们现在知道脂质双层积极参与了许多这些细胞事件，而不是仅仅溶解膜蛋白，而是对其生物物理和材料特征产生了重新兴趣。但是，当前研究重点的许多事件 - 囊泡，分选，内吞，感应，运动等 - 发生在长度和相关的时间尺度上，这些时间量表显着超出了原子分子模拟技术的范围。因此，已经很大的兴趣致力于开发粗粒模型，这些模型减少了所需的自由度的数量，并能够对现象的系统研究，这些现象主要与化学细节无关[1]。其中，消除了嵌入溶剂的需求的模型最终是最大的承诺，即最终将间隙弥合到细胞器级别[2]，但它们仍然是模拟工具箱的最新补充，需要进一步研究。 PI最近开发了一种高度粗粒的无溶剂脂质模型[3]，并成功地将其应用于涉及组成狂热偶联[4]和曲率介导的相互作用[5]的问题。虽然坚固地代表大型膜特性，但它的解决方案不足以说明结构双层细节，这对于脂质 - 蛋白质相互作用的几个方面很重要。为了使差距向后弥合脂质的更详细的描述，PI建议仔细重新引入自由度和脂质物种个性，同时保持嵌入溶剂的隐式。该计划是遵循基于结构的粗（或细）栅格技术，该技术将现有原子和介观量表与溶剂自由领域联系起来。这种方法尤其需要重要的计算能力才能在细节级别上获得非常好的结构统计数据，从而需要访问超级计算设施。 DAC框架内授予的CPU时间既将是最初的系统启动，更重要的是 - 有助于获得至关重要的经验，并扩展了制定随后的MRAC建议所需的信息。 [1] M. Muller，K。Katsov和M. Schick，“生物学和合成膜：从粗粒描述中可以学到什么？”，物理。 Rep。_434_，113（2006）; M. Venturoli，M.M。 Sperotto，M。Kranenburg和B. Smit，“生物膜的介观模型”，物理学。 Rep。_437_，1（2006）。 [2] G. Brannigan，L.C.L。 Lin和F.L.H Brown，“生物膜的隐式溶剂模拟模型”，Eur。生物。 J. _35_，104（2006）。 [3] I.R. Cooke，K。Kremer和M. Deserno，“流体双层膜的可调通用模型”，物理。 Rev. E _72_，011506（2005）; I.R. Cooke和M. Deserno，“用于自组装流体双层膜的无溶剂模型：基于宽阔的尾巴电势的流体相稳定”，J。Chem。物理。 _123_，224710（2005）。 [4] I.R. Cooke和M. Deserno，“脂质形状和膜曲率之间的耦合”，生物植物。 J. _91_，487（2006）。 [5] B.J. Reynwar，G。Illya，V.A。 Harmandaris，M.M。穆勒（K.