Prediction and characterization of liquid-liquid phase separation of minimalistic peptides

Yiming Tang, Santu Bera, Yifei Yao, Jiyuan Zeng, Zenghui Lao, Xuewei Dong, Ehud Gazit*, Guanghong Wei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Liquid-liquid phase separation (LLPS) of proteins mediates the assembly of biomolecular condensates involved in physiological and pathological processes. Identifying the minimalistic building blocks and the sequence determinant of protein phase separation is an urgent need but remains challenging partially due to lack of methodologies to characterize the phase behavior. Here, we demonstrate computational tools to efficiently quantify the microscopic fluidity of liquid condensates and the temperature-dependent phase diagram of peptides. We comprehensively explore the LLPS abilities of all 400 dipeptide combinations of coded amino acids and observe the occurrences of spontaneous LLPS in three categories of dipeptides. Our predictions are validated by turbidity assays and differential interference contrast (DIC) microscopy. We demonstrate that dipeptides, minimal but complete, possess multivalent interactions sufficient for LLPS, suggesting LLPS is a general property of peptides and proteins, independent of their sequence length. This study paves the way for the prediction and characterization of peptide phase behavior at the molecular level.

Original languageEnglish
Article number100579
JournalCell Reports Physical Science
Volume2
Issue number9
DOIs
StatePublished - 22 Sep 2021

Funding

FundersFunder number
National Supercomputer Centre in Guangzhou
National Natural Science Foundation of China12074079
Fudan University
Israel Science Foundation3145/19
National Key Research and Development Program of China2016YFA0501702

    Keywords

    • Martini forcefield
    • coarse-grained model
    • dipeptide
    • liquid-liquid phase separation
    • minimalistic peptide
    • molecular dynamics simulation
    • phase diagram

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