Molecular Simulations of Biological Active Matter

来自马里兰大学帕克分校的Garegin Papoian教授获得了化学系化学理论，模型和计算方法项目的奖项，以促进对活性物质的理论理解和计算建模。后者从根本上不同于传统的物质状态，如固体，液体和气体。在活性物质系统中，单个粒子消耗能量，推动它们沿着方向运动，这些机动粒子的相互作用导致各种各样的远离平衡态的奇异行为。细胞是迄今为止最重要的活性物质的例子，其中化学和力学强烈耦合，例如，允许细胞四处爬行并主动感知细胞外环境。Papoian教授的团队一直在开发一种名为MEDYAN的新型研究平台，该平台可以对复杂的活性物质系统进行计算机模拟。Papoian教授的实验室将在MEDYAN中研究细胞骨架细丝的新表示，预计细胞骨架网络的各种非线性变形建模的复杂性将大大增加。他的团队将开发考虑可变形膜上化学动力学的算法，这反过来将能够模拟许多有趣的细胞过程，如受体聚集和细胞信号传导。从长远来看，MEDYAN的开发将为以单分子分辨率对整个细胞进行计算机建模铺平道路。主要研究者还继续开展各种教育和推广活动，特别是担任美国国家化学奥林匹克高中生队的物理化学讲师。Papoian教授的方法基于他的小组开发的一种新的模拟框架，称为MEDYAN（主动网络的机械化学动力学）。它是一个高度复杂的反应力场，针对微米级复杂分子系统，例如包含各种化学物质和聚合物混合物的可变形囊泡。MEDYAN将化学动力学与机械平衡相结合，全面涵盖了细胞骨架的许多重要组成部分。Papoian教授的团队将依靠复杂的非线性弹性理论来描述MEDYAN中的细胞骨架丝，从而首次实现大型细胞骨架网络中扭转和手性效应的基于结构的研究。特别是，Papoian教授的实验室将研究肌动蛋白丝在纳米尺度下的手性如何传播到微米尺度，这可能导致旋转对称性破缺。在另一个项目中，他们正在开发用于模拟膜歧管上的反应扩散过程的算法，以实现表面和内部化学之间的仔细区分。这种能力使得能够研究各种各样令人兴奋的生物现象，从导致管状突起形成的曲率诱导蛋白质的聚集到免疫细胞中的信号受体聚集。MEDYAN已被许多研究小组卓有成效地用于模拟各种活性物质现象，从软物质到细胞生物学。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Professor Garegin Papoian from the University of Maryland-College Park is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to advance theoretical understanding and computational modeling of active matter. The latter is fundamentally different from traditional states of matter, such as solids, liquids, and gases. In active matter systems, the individual particles consume energy, propelling them along directional motions, where the mutual interactions of these motorized particles lead to a wide variety of far-from-equilibrium phases with exotic behaviors. The cell is by far the most important example of active matter, where chemistry and mechanics are strongly coupled, for example, allowing the cell to crawl around and actively sense the extracellular environment. Prof. Papoian’s group has been developing a novel research platform, called MEDYAN, which enables computer simulations of complex active matter systems. Prof. Papoian’s laboratory will work on a new representation of cytoskeletal filaments within MEDYAN, anticipating great increase in the sophistication of modeling of various nonlinear deformations of cytoskeletal networks. His group will develop algorithms that take into account chemistry dynamics on deformable membranes, which, in turn, will enable simulations of many interesting cellular processes, such as receptor clustering and cellular signaling. Longer-term, the development of MEDYAN will pave the way for in silico modeling of the whole cell at a single molecule resolution. The PI is also continuing his various educational and outreach activities, in particular, serving as physical chemistry lecturer for the US National Chemistry Olympiad Team of high school students.Prof. Papoian’s approach is based on a novel simulation framework developed in his group, called MEDYAN (the Mechanochemical Dynamics of Active Networks). It is a highly intricate reactive force field, targeted at micrometer scale complex molecular systems, such as deformable vesicles containing a mixture of various chemical species and polymers. MEDYAN interleaves chemical dynamics with mechanical equilibration, comprehensively covering in particular many important components of the cellular cytoskeleton. Prof. Papoian’s group will rely on a sophisticated nonlinear elasticity theory to describe cytoskeletal filaments in MEDYAN, enabling, for the first-time, structure-based studies of torsional and chiral effects in large cytoskeletal networks. In particular, Prof. Papoian’s laboratory will investigate how the chirality of actin filaments at the nanometer scale may propagate to the micrometer scale, which may lead to rotational symmetry breaking. In a different project, they are developing algorithms for simulating reaction-diffusion processes on the membrane manifold, achieving a careful distinction between surface and interior chemistries. This capability enables studies of a wide variety of exciting biological phenomena, from the aggregation of curvature inducing proteins causing formation of tubular protrusions to signaling receptor clustering in immune cells. MEDYAN has been fruitfully used by many research groups to model a variety of active matter phenomena, from soft matter to cell biology. The ongoing developments will further broaden its appeal, from various new researches to high school demonstrations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.