Chaperons Against Self-Association for Phase-Separating RNA-Binding Proteins

Yoshizawa, Takuya

doi:10.1007/978-981-99-4886-4_4

Phase Separation in Living Cells 2023

DOI: 10.1007/978-981-99-4886-4_4

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Chaperons Against Self-Association for Phase-Separating RNA-Binding Proteins

Takuya Yoshizawa

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2024

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Harnessing Transformers to Generate Protein Sequences Prone to Liquid Liquid Phase Separation

Wasim,

Pramanik,

Das

et al. 2024

Preprint

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In this study, we delve into the intricate molecular language of Intrinsically Disordered Proteins (IDPs) using specialized transformer neural network-based language models, specifically GPT models, pre-trained on sequences exhibiting varying propensities for liquid-liquid phase separation (LLPS). Our approach encompasses the development of distinct models tailored for proteins highly predisposed to LLPS (LLPS+), those with moderate LLPS potential (LLPS-), and folded proteins resistant to LLPS (PDB*). Through the generation of 18,000 sequences, evenly distributed among the three model types, a majority of which demonstrate minimal similarity to proteins cataloged in the SwissProt database, we derive residue-level transition probability matrices. These matrices offer a probabilistic insight into the amino acid grammar unique to each dataset. Analysis of local sequence properties reveals the potential of sequences from LLPS+ GPT models to undergo phase separation. Subsequent validation through multi-chain simulations further substantiates the phase separating potential of the generated proteins and the generation of phase separating sequences from LLPS+ GPT. Additionally, we introduce and train a classifier capable of discerning whether a given amino acid sequence is prone to LLPS. This comprehensive investigation elucidates the molecular grammar of proteins, facilitating the integration of advanced computational methodologies with practical applications in generating protein sequences with desired phenotype.

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Harnessing Transformers to Generate Protein Sequences Prone to Liquid Liquid Phase Separation

Wasim,

Pramanik,

Das

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Chaperons Against Self-Association for Phase-Separating RNA-Binding Proteins

Cited by 1 publication

References 49 publications

Harnessing Transformers to Generate Protein Sequences Prone to Liquid Liquid Phase Separation

Harnessing Transformers to Generate Protein Sequences Prone to Liquid Liquid Phase Separation

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