{"title":"Emergence of Multiphase Condensates from a Limited Set of Chemical Building Blocks.","authors":"Fan Chen, William M Jacobs","doi":"10.1021/acs.jctc.4c00323","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.jctc.4c00323","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.