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).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 脂质双层是所有活细胞的关键结构组分之一。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结构域之间的物质和信号的受控运输中发挥关键作用。而不仅仅是溶解膜蛋白，因为一直认为，我们现在知道，脂质双层积极参与许多这些细胞的事件，这已经产生了新的兴趣，在其生物物理和材料特性。然而，目前的研究重点的许多事件-泡囊形成，排序，内吞作用，传感，运动等-发生的长度和相关的时间尺度，这是显着超出了原子分子模拟技术的范围。因此，人们对开发粗粒度模型非常感兴趣，这些模型减少了所需自由度的数量，并能够系统地研究在很大程度上与化学细节无关的现象[1]。其中，消除包埋溶剂的模型最有希望最终将差距缩小到细胞器水平[2]，但它们仍然是模拟工具箱中的一个新成员，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组成-曲率耦合[4]和曲率介导的相互作用[5]的问题。虽然强有力地代表大规模的膜特性，它是不够精细地解决占结构双层的细节，重要的几个方面的脂质-蛋白质相互作用。为了弥合差距，向后更详细地描述脂质，PI建议小心地重新引入自由度和脂质种类的个性，同时保持包埋溶剂的隐含性。该计划是遵循基于结构的粗（或细）粒化技术，将现有的原子和介观尺度与无溶剂领域联系起来。这种方法尤其需要强大的计算能力，才能在更精细的细节层次上获得非常好的结构统计数据，因此需要使用超级计算设施。在DAC框架内授予的CPU时间将作为初始系统启动，更重要的是，有助于获得制定后续MRAC建议所需的关键经验和扩展信息。[1]M. Muller，K. Katsov和M.生物和合成膜：从粗粒度描述中可以学到什么？434_，113（2006）; M. Venturoli，M.M. Sperotto，M. Kranenburg和B. Smit，“Mesoscopic models of biological membranes”，Phys.Rep._437_，1（2006）. [2]G. Brannigan，L.C.L. Lin和F.L.H. Brown，“Implicit solvent simulation models for biomembranes”，Eur. Biophys. J._35_，104（2006）. [3]I.R.库克，K。Kremer和M. L.R.，“Tunable generic model for fluid bilayer membranes”，Phys.Rev.E_72_，011506（2005）; I.R. Cooke和M. Alberno，“Solvent-free model for self-assembled fluid bilayer membranes：Stabilization of the fluid phase based on broad attractive tail potential”，J.Chem.Phys._123_，224710（2005）。[4]I.R. Cooke和M. Alberno，“Coupling between lipid shape and membrane curvature”，Biophys. J._91_，487（2006）. [5]B. J.埃斯库瓦，G.伊利亚Harrisis，M. M. Muller，K. Kremer和M. Alberno，“Aggregation and vesiculation of membrane proteins by curvature-mediated interactions”，Nature _447_，461-464（2007）.