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Abstract We have developed an algorithm, ParSe, which accurately identifies from the primary sequence those protein regions likely to exhibit physiological phase separation behavior. Originally, ParSe was designed to test the hypothesis that, for flexible proteins, phase separation potential is correlated to hydrodynamic size. While our results were consistent with that idea, we also found that many different descriptors could successfully differentiate between three classes of protein regions: folded, intrinsically disordered, and phase‐separating intrinsically disordered. Consequently, numerous combinations of amino acid property scales can be used to make robust predictions of protein phase separation. Built from that finding, ParSe 2.0 uses an optimal set of property scales to predict domain‐level organization and compute a sequence‐based prediction of phase separation potential. The algorithm is fast enough to scan the whole of the human proteome in minutes on a single computer and is equally or more accurate than other published predictors in identifying proteins and regions within proteins that drive phase separation. Here, we describe a web application for ParSe 2.0 that may be accessed through a browser by visitinghttps://stevewhitten.github.io/Parse_v2_FASTAto quickly identify phase‐separating proteins within large sequence sets, or by visitinghttps://stevewhitten.github.io/Parse_v2_webto evaluate individual protein sequences.
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The blobulator: a webtool for identification and visual exploration of hydrophobic modularity in protein sequences
Clusters of hydrophobic residues are known to promote structured protein stability and drive protein aggregation. Recent work has shown that identifying contiguous hydrophobic residue clusters (termed “blobs”) has proven useful in both intrinsically disordered protein (IDP) simulation and human genome studies. However, a graphical interface was unavailable. Here, we present the blobulator: an interactive and intuitive web interface to detect intrinsic modularity in any protein sequence based on hydrophobicity. We demonstrate three use cases of the blobulator and show how identifying blobs with biologically relevant parameters provides useful information about a globular protein, two orthologous membrane proteins, and an IDP. Other potential applications are discussed, including: predicting protein segments with critical roles in tertiary interactions, providing a definition of local order and disorder with clear edges, and aiding in predicting protein features from sequence. The blobulator GUI can be found atwww.blobulator.branniganlab.org, and the source code with pip installable command line tool can be found on GitHub at www.GitHub.com/BranniganLab/blobulator.
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- Award ID(s):
- 2152059
- PAR ID:
- 10533901
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Posted Content:
- https://doi.org/10.1101/2024.01.15.575761
