Chaisson Emily H, Heberle Frederick A, Doktorova Milka
Department of Chemistry, University of Tennessee Knoxville, Knoxville, Tennessee 37996, United States.
Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, SE-171 65 Solna, Sweden.
J Chem Inf Model. 2025 Apr 28;65(8):3879-3885. doi: 10.1021/acs.jcim.4c02287. Epub 2025 Apr 16.
In a lipid bilayer, the interactions between the lipid hydrocarbon chains from opposing leaflets can influence membrane properties. These interactions include the phenomenon of interdigitation, in which an acyl chain of one leaflet extends past the bilayer midplane and into the opposing leaflet. While static interdigitation is well understood in gel-phase bilayers from X-ray diffraction measurements, much less is known about dynamic interdigitation in fluid phases. In this regard, atomistic molecular dynamics simulations can provide mechanistic information on interleaflet interactions that can be used to generate experimentally testable hypotheses. To address limitations of existing computational methodologies that provide results that are either indirect or averaged over time and space, here we introduce three novel ways of quantifying the extent of chain interdigitation. Our protocols include the analysis of instantaneous interactions at the level of individual carbon atoms, thus providing temporal and spatial resolution for a more nuanced picture of dynamic interdigitation. We compare the methods on bilayers composed of lipids with an equal total number of carbon atoms, but different mismatches between the -1 and -2 chain lengths. We find that these metrics, which are based on freely available software packages and are easy to implement, provide complementary details that help characterize various features of lipid-lipid contacts at the bilayer midplane. The new frameworks thus allow for a deeper look at fundamental molecular mechanisms underlying bilayer structure and dynamics and present a valuable expansion of the membrane biophysics toolkit.
在脂质双分子层中，相对小叶的脂质烃链之间的相互作用会影响膜的性质。这些相互作用包括交叉指状化现象，即一个小叶的酰基链延伸穿过双分子层中间平面并进入相对的小叶。虽然通过X射线衍射测量在凝胶相双分子层中对静态交叉指状化已经有了很好的理解，但对于流体相中的动态交叉指状化了解得要少得多。在这方面，原子分子动力学模拟可以提供关于小叶间相互作用的机制信息，可用于生成实验可测试的假设。为了解决现有计算方法的局限性，这些方法提供的结果要么是间接的，要么是在时间和空间上平均的，在这里我们介绍三种量化链交叉指状化程度的新方法。我们的方案包括在单个碳原子水平上分析瞬时相互作用，从而为动态交叉指状化提供更细致入微的时间和空间分辨率图像。我们在由碳原子总数相等但-1链长和-2链长之间错配不同的脂质组成的双分子层上比较这些方法。我们发现，这些基于免费软件包且易于实现的指标提供了互补的细节，有助于表征双分子层中间平面脂质-脂质接触的各种特征。因此，这些新框架能够更深入地了解双分子层结构和动力学背后的基本分子机制，并为膜生物物理学工具包提供了有价值的扩展。
