Computational Design of Self-Assembling Peptide Chassis Materials for Synthetic Cells
Computational Design of Self-Assembling Peptide Chassis Materials for Synthetic Cells
复制标题
合成细胞自组装肽底盘材料的计算设计
DOI：
10.1039/d2me00169a
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Ferguson, Andrew L
中科院分区：
文献类型：
--
作者：
Ma, Yutao;Kapoor, Rohan;Sharma, Bineet;Liu, Allen;Ferguson, Andrew L
巨脂囊泡已被广泛用作合成细胞模型，以再现各种类似生命的过程，包括体外蛋白质合成，DNA复制和细胞骨架组织。细胞大小的脂质囊泡本质上是机械脆弱的，并且由于渗透应力而易于破裂，这限制了它们的可用性。最近，肽囊泡已被引入作为合成细胞的替代底盘材料，其比脂质囊泡更坚固和稳定，并且可以承受苛刻的条件，包括pH、热和渗透变化。在这项工作中，我们结合联合收割机粗粒度的分子模拟，增强采样自由能计算，高斯过程回归，贝叶斯优化构建一个主动学习筛选的二嵌段两亲性弹性蛋白样多肽能够形成化学稳定的囊泡结构，适合于自组装的合成肽囊泡。我们的计算筛选确定了许多有前途的序列，这些序列形成相对于本体溶剂中的分离肽具有高热力学稳定性的肽囊泡，每个氨基酸残基约为10- 15 kBT。
Giant lipid vesicles have been used extensively as a synthetic cell model to recapitulate various life-like processes, including in vitro protein synthesis, DNA replication, and cytoskeleton organization. Cell-sized lipid vesicles are mechanically fragile in nature and prone to rupture due to osmotic stress, which limits their usability. Recently, peptide vesicles have been introduced as an alternative chassis material for synthetic cells that are more robust and stable than lipid vesicles, and can withstand harsh conditions including pH, thermal, and osmotic variations. In this work, we combine coarse-grained molecular simulation, enhanced sampling free energy calculations, Gaussian process regression, and Bayesian optimization to construct an active learning screening for diblock amphiphilic elastin-like polypeptides capable of forming thermodynamically stable vesicular structures suitable for the self-assembly of synthetic peptide vesicles. Our computational screen identifies a number of promising sequences that form peptidic vesicles with high thermodynamic stabilities relative to isolated peptides in bulk solvent on the order of 10–15kBT per amino acid residue.