Dataset Information

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

ABSTRACT: Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block copolymers. Herein, we present new peptide amphiphiles composed of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules, termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications.

SUBMITTER: Jacoby G

PROVIDER: S-EPMC8397319 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

Jacoby Guy G Segal Asher Merav M Ehm Tamara T Abutbul Ionita Inbal I Shinar Hila H Azoulay-Ginsburg Salome S Zemach Ido I Koren Gil G Danino Dganit D Kozlov Michael M MM Amir Roey J RJ Beck Roy R

Journal of the American Chemical Society 20210726 30

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of ...[more]

PMID: 34310121

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Project description:The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP/IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents 'Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55 vs. 27%) with a much higher precision on an independent data set. The current study also sheds some light on a possible 'disorder-to-order' transitioning consensus, untangled, yet embedded in the amino acid sequence of IDPs. Some guidelines have also been suggested for proceeding with a real-life structural modeling involving an IDPR using Proteus.

Dataset Information

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

Publications

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

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