Whether lipid rafts are present in the membranes of living cells remains hotly disputed despite their incontrovertible existence in liposomes at 298 K. In attempts to resolve this debate, molecular dynamics (MD) simulations have been extensively used to study lipid phase separation at high resolution. However, computation has been of limited utility in this respect because the experimental distributions of phases in lamellar lipid mixtures are poorly reproduced by simulations. In particular, all-atom (AA) approaches suffer from restrictions on accessible time scales and system sizes whereas the more efficient coarse-grained (CG) force fields remain insufficiently accurate to achieve correspondence with experiment. In this work, we refine the CG Martini parameters for the high- and low-melting temperature (T_m) lipids 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). Our approach involves the modification of bonded Martini parameters based on fitting to atomistic simulations conducted with the CHARMM36 lipid force field. The resulting CG parameters reproduce experimental structural and thermodynamic properties of homogeneous lipid membranes while concurrently improving simulation fidelity to experimental phase diagrams of DPPC, DOPC, and cholesterol lipid mixtures. Importantly, the refined parameters provide much better phase accuracy for regions near the critical point that mimic the lipid concentrations under physiological conditions.

中文翻译：

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用精细马提尼粗粒力场捕获三元脂质混合物的相行为

尽管在298 K脂质体中存在不可逆的脂质筏，但活细胞膜中是否存在脂质筏仍然是一个备受争议的问题。为了解决这一争论，分子动力学（MD）模拟已广泛用于高分辨率研究脂质相分离。但是，计算在这方面用途有限，因为通过模拟很难再现层状脂质混合物中相的实验分布。特别是，全原子（AA）方法受到可访问的时间尺度和系统大小的限制，而更有效的粗粒度（CG）力场仍然不够准确，无法实现与实验的一致性。在这项工作中，我们针对高熔点和低熔点（T _m）脂质1,2-二棕榈酰基-sn-甘油-3-磷脂酰胆碱（DPPC）和1,2-二油酰基-sn-甘油-3-磷脂酰胆碱（DOPC）。我们的方法涉及基于对使用CHARMM36脂质力场进行的原子模拟的拟合，修改键合马提尼参数的方法。所得的CG参数再现了均质脂质膜的实验结构和热力学性质，同时提高了DPPC，DOPC和胆固醇脂质混合物的实验相图的模拟保真度。重要的是，对于在生理条件下模仿脂质浓度的临界点附近的区域，精确的参数可提供更好的相位精度。