Chen Fan, Jacobs William M
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
J Chem Theory Comput. 2024 Aug 13;20(15):6881-6889. doi: 10.1021/acs.jctc.4c00323. Epub 2024 Jul 30.
Biomolecules composed of a limited set of chemical building blocks can colocalize into distinct, spatially segregated compartments known as biomolecular condensates. While many condensates are known to form spontaneously via phase separation, it has been unclear how immiscible condensates with precisely controlled molecular compositions assemble from a small number of chemical building blocks. We address this question by establishing a connection between the specificity of biomolecular interactions and the thermodynamic stability of coexisting condensates. By computing the minimum interaction specificity required to assemble condensates with target molecular compositions, we show how to design heteropolymer mixtures that produce compositionally complex condensates by using only a small number of monomer types. Our results provide insight into how compositional specificity arises in naturally occurring multicomponent condensates and demonstrate a rational algorithm for engineering complex artificial condensates from simple chemical building blocks.
由有限的一组化学构建单元组成的生物分子可以共定位到称为生物分子凝聚物的不同的、空间上隔离的区室中。虽然已知许多凝聚物通过相分离自发形成，但尚不清楚具有精确控制的分子组成的互不相溶的凝聚物如何从少量化学构建单元组装而成。我们通过建立生物分子相互作用的特异性与共存凝聚物的热力学稳定性之间的联系来解决这个问题。通过计算组装具有目标分子组成的凝聚物所需的最小相互作用特异性，我们展示了如何设计仅使用少量单体类型就能产生组成复杂的凝聚物的杂聚物混合物。我们的结果为天然存在的多组分凝聚物中组成特异性的产生提供了见解，并展示了一种从简单化学构建单元设计复杂人工凝聚物的合理算法。
