disordered peptides
Recently Published Documents


TOTAL DOCUMENTS

43
(FIVE YEARS 10)

H-INDEX

12
(FIVE YEARS 0)

2021 ◽  
Author(s):  
Maryam Rahmati ◽  
Sabine Stötzel ◽  
Thaqif El Khassawna ◽  
Chenyi Mao ◽  
Adilijiang Ali ◽  
...  

2021 ◽  
Vol 22 (20) ◽  
pp. 11058
Author(s):  
Ellen Rieloff ◽  
Marie Skepö

Intrinsically disordered proteins are involved in many biological processes such as signaling, regulation, and recognition. A common strategy to regulate their function is through phosphorylation, as it can induce changes in conformation, dynamics, and interactions with binding partners. Although phosphorylated intrinsically disordered proteins have received increased attention in recent years, a full understanding of the conformational and structural implications of phosphorylation has not yet been achieved. Here, we present all-atom molecular dynamics simulations of five disordered peptides originated from tau, statherin, and β-casein, in both phosphorylated and non-phosphorylated state, to compare changes in global dimensions and structural elements, in an attempt to gain more insight into the controlling factors. The changes are in qualitative agreement with experimental data, and we observe that the net charge is not enough to predict the impact of phosphorylation on the global dimensions. Instead, the distribution of phosphorylated and positively charged residues throughout the sequence has great impact due to the formation of salt bridges. In statherin, a preference for arginine–phosphoserine interaction over arginine–tyrosine accounts for a global expansion, despite a local contraction of the phosphorylated region, which implies that also non-charged residues can influence the effect of phosphorylation.


2021 ◽  
Vol 22 (18) ◽  
pp. 10174
Author(s):  
Ellen Rieloff ◽  
Marie Skepö

Phosphorylation is a common post-translational modification among intrinsically disordered proteins and regions, which helps regulate function by changing the protein conformations, dynamics, and interactions with binding partners. To fully comprehend the effects of phosphorylation, computer simulations are a helpful tool, although they are dependent on the accuracy of the force field used. Here, we compared the conformational ensembles produced by Amber ff99SB-ILDN+TIP4P-D and CHARMM36m, for four phosphorylated disordered peptides ranging in length from 14–43 residues. CHARMM36m consistently produced more compact conformations with a higher content of bends, mainly due to more stable salt bridges. Based on comparisons with experimental size estimates for the shortest and longest peptide, CHARMM36m appeared to overestimate the compactness. The difference between the force fields was largest for the peptide showing the greatest separation between positively charged and phosphorylated residues, in line with the importance of charge distribution. For this peptide, the conformational ensemble did not change significantly upon increasing the ionic strength from 0 mM to 150 mM, despite a reduction of the salt-bridging probability in the CHARMM36m simulations, implying that salt concentration has negligible effects in this study.


2021 ◽  
Author(s):  
Lunna Li ◽  
Tommaso Casalini ◽  
Paolo Arosio ◽  
Matteo Salvalaglio

Intrinsically disordered proteins (IDPs) play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure-function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and forcefields. Nevertheless, differences in fine details emerge from varying forcefield/sampling method combinations. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which can be common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field/enhanced sampling method combinations for accurate structural and thermodynamic information in the study of general disordered proteins.


2021 ◽  
Author(s):  
Guy Jacoby ◽  
Merav Segal Asher ◽  
Tamara Ehm ◽  
Inbal Abutbul-Ionita ◽  
Hila Shinar ◽  
...  

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 comprised 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.


2021 ◽  
Author(s):  
Guy Jacoby ◽  
Merav Segal Asher ◽  
Tamara Ehm ◽  
Inbal Abutbul-Ionita ◽  
Hila Shinar ◽  
...  

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 comprised 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.


2021 ◽  
Author(s):  
Pablo G. Argudo ◽  
Juan J. Giner-Casares

Proteins and peptide fragments are highly relevant building blocks in self-assembly for nanostructures with plenty of applications.


Sign in / Sign up

Export Citation Format

Share Document