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: 7956253
• 负责人: Markus Deserno
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956253
• 关键词: Accounting; Award; Biochemical; Biological; Biological Models; Biomedical Research; Cells; Cereals; Characteristics; Chemicals; Classification; Computer Retrieval of Information on Scientific Projects Database; Coupling; Development; Endocytosis; Environment; Event; Freedom; Funding; Generic Drugs; Grant; High Performance Computing; 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).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 脂质双层是所有活细胞的关键结构组成部分之一。它们将细胞生化环境划分和组织成细胞器，并在介导空间分离的域之间的物质和信号的受控运输中发挥关键作用。我们现在知道，脂质双层积极参与许多这些细胞事件，而不是像人们长期以来所认为的那样仅仅溶解膜蛋白，这引起了人们对其生物物理和材料特性的新兴趣。然而，当前研究关注的许多事件——囊泡形成、分类、内吞作用、传感、运动等——发生在长度和相关的时间尺度上，这远远超出了原子分子模拟技术的范围。因此，人们对粗粒度模型的开发产生了很大的兴趣，这些模型可以减少所需的自由度数量，并能够对很大程度上独立于化学细节的现象进行系统研究[1]。其中，无需嵌入溶剂的模型最有希望最终弥合细胞器水平的差距[2]，但它们仍然是模拟工具箱中的最新成员，需要进一步研究。 PI 最近开发了一种高度粗粒度的无溶剂脂质模型 [3]，并成功地将其应用于涉及成分-曲率耦合 [4] 和曲率介导的相互作用 [5] 的问题。虽然有力地代表了大规模的膜特性，但它的分辨率还不够精细，无法解释对脂质-蛋白质相互作用的几个方面很重要的结构双层细节。为了缩小对脂质更详细描述的差距，PI 建议仔细地重新引入自由度和脂质种类的个性，同时保持嵌入溶剂的隐含性。该计划是遵循基于结构的粗（或细）晶粒技术，将现有的原子和介观尺度与无溶剂领域联系起来。这种方法特别需要大量的计算能力来获得更精细的结构统计数据，因此需要使用超级计算设施。在 DAC 框架内授予的 CPU 时间将用作初始系统启动，更重要的是，有助于获得制定后续 MRAC 提案所需的关键经验和扩展信息。 [1] M. Muller、K. Katsov 和 M. Schick，“生物膜和合成膜：从粗粒度描述中可以学到什么？”，Phys。众议员_434_, 113 (2006); M.文图罗利，M.M. Sperotto、M. Kranenburg 和 B. Smit，“生物膜的介观模型”，Phys。众议员_437_，1 (2006)。 [2] G. 布兰尼根，L.C.L. Lin 和 F.L.H Brown，“生物膜的隐式溶剂模拟模型”，Eur。生物物理学。 J._35_，104（2006）。 [3] I.R. Cooke、K. Kremer 和 M. Deserno，“流体双层膜的可调谐通用模型”，Phys。修订版 E _72_，011506 (2005)；红外线Cooke 和 M. Deserno，“自组装流体双层膜的无溶剂模型：基于广泛有吸引力的尾部电位的流体相稳定”，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”，Biophys。 J._91_，487（2006）。 [5] B.J. Reynwar、G. Illya、V.A.哈曼达里斯，M.M. Muller、K. Kremer 和 M. Deserno，“通过曲率介导的相互作用实现膜蛋白的聚集和囊泡化”，Nature _447_，461-464 (2007)。