Membrane potential drives direct translocation of cell-penetrating peptides

Nanoscale ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 1949-1958 ◽  
Author(s):  
Xinli Gao ◽  
Song Hong ◽  
Zhiping Liu ◽  
Tongtao Yue ◽  
Jure Dobnikar ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Membrane Potential ◽  
Electrostatic Potential ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

We report the molecular dynamics evidence for the direct translocation of CPPs across the membrane driven by the membrane electrostatic potential.

scholarly journals Effects of Membrane Potential on the Entry of Cell-Penetrating Peptides Transportan 10 into Single Vesicles

2020 ◽  
Vol 118 (3) ◽  
pp. 234a
Author(s):  
Md. Mizanur R. Moghal ◽  
Md. Zahidul Islam ◽  
Farzana Hossain ◽  
Samiron Kumar Saha ◽  
Masahito Yamazaki
Keyword(s):  
Membrane Potential ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals Peptide-Ligand Binding Modeling of siRNA with Cell-Penetrating Peptides

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Alfonso T. García-Sosa ◽  
Indrek Tulp ◽  
Kent Langel ◽  
Ülo Langel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Binding Affinity ◽  
Cell Penetrating Peptides ◽  
Peptide Ligand ◽  
Intermolecular Hydrogen Bonds ◽  
Cell Penetrating ◽  
The Stability ◽  
Dynamics Simulations ◽  
Explicit Water

The binding affinity of a series of cell-penetrating peptides (CPP) was modeled through docking and making use of the number of intermolecular hydrogen bonds, lipophilic contacts, and the number of sp3 molecular orbital hybridization carbons. The new ranking of the peptides is consistent with the experimentally determined efficiency in the downregulation of luciferase activity, which includes the peptides’ ability to bind and deliver the siRNA into the cell. The predicted structures of the complexes of peptides to siRNA were stable throughout 10 ns long, explicit water molecular dynamics simulations. The stability and binding affinity of peptide-siRNA complexes was related to the sidechains and modifications of the CPPs, with the stearyl and quinoline groups improving affinity and stability. The reranking of the peptides docked to siRNA, together with explicit water molecular dynamics simulations, appears to be well suited to describe and predict the interaction of CPPs with siRNA.

scholarly journals Using molecular dynamics simulations to prioritize and understand AI-generated cell penetrating peptides

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Duy Phuoc Tran ◽  
Seiichi Tada ◽  
Akiko Yumoto ◽  
Akio Kitao ◽  
Yoshihiro Ito ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
De Novo ◽  
Homology Modelling ◽  
Md Simulations ◽  
Cell Penetrating Peptides ◽  
Generative Models ◽  
Cell Penetrating ◽  
Wet Lab ◽  
Dynamics Simulations ◽  
De Novo Peptide

AbstractCell-penetrating peptides have important therapeutic applications in drug delivery, but the variety of known cell-penetrating peptides is still limited. With a promise to accelerate peptide development, artificial intelligence (AI) techniques including deep generative models are currently in spotlight. Scientists, however, are often overwhelmed by an excessive number of unannotated sequences generated by AI and find it difficult to obtain insights to prioritize them for experimental validation. To avoid this pitfall, we leverage molecular dynamics (MD) simulations to obtain mechanistic information to prioritize and understand AI-generated peptides. A mechanistic score of permeability is computed from five steered MD simulations starting from different initial structures predicted by homology modelling. To compensate for variability of predicted structures, the score is computed with sample variance penalization so that a peptide with consistent behaviour is highly evaluated. Our computational pipeline involving deep learning, homology modelling, MD simulations and synthesizability assessment generated 24 novel peptide sequences. The top-scoring peptide showed a consistent pattern of conformational change in all simulations regardless of initial structures. As a result of wet-lab-experiments, our peptide showed better permeability and weaker toxicity in comparison to a clinically used peptide, TAT. Our result demonstrates how MD simulations can support de novo peptide design by providing mechanistic information supplementing statistical inference.

Effect of the electrostatic potential on the internalization mechanism of cell penetrating peptides derived from TIRAP

2012 ◽  
Vol 17 (3) ◽  
pp. 485-499 ◽  
Author(s):  
Karen A. Flores ◽  
J. Cristian Salgado ◽  
Gerald Zapata-Torres ◽  
Ziomara P. Gerdtzen ◽  
María-Julieta Gonzalez ◽  
...  
Keyword(s):  
Electrostatic Potential ◽  
Cell Penetrating Peptides ◽  
Internalization Mechanism ◽  
Cell Penetrating

scholarly journals Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes

2021 ◽  
Author(s):  
Joan Gimenez-Dejoz ◽  
Keiji Numata
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Biological Membranes ◽  
Cell Penetrating Peptides ◽  
Delivery Systems ◽  
Cell Penetrating ◽  
Target Molecules

Peptide-based delivery systems that deliver target molecules into cells have been gaining traction. These systems need cell-penetrating peptides (CPPs), which have the remarkable ability to penetrate into biological membranes and...

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