[Soft-matter] Soft Matter & Complex Systems Seminar on 18 Oct 2024

[Maciej Lisicki]

Dear Soft Matter & Complex Systems Colleagues and Friends,

On Friday 18 October 2024 at 9:30 AM at the UW Faculty of Physics (Pasteura 5, Warsaw; room 1.40) we are hosting a seminar during which 

Krzysztof Kuczera (Department of Chemistry and2Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA)

will give a talk
Discovery and Characterization of Blood-Brain Barrier Modulating Peptides based on E-cadherin

Abstract

The delivery of pharmaceutical agents to the central nervous system is hindered by the Blood-Brain Barrier (BBB), a network of inter-cellular interactions of the epithelium. Here, we present a search for novel peptides able to modulate the BBB, focusing on the E-cadherin protein, which is involved in the formation of these intercellular junctions. Previously, two classes of peptides, HAV and ADT, were known to modulate BBB permeability in vitro and in vivo. Here we use computational methods to perform a systematic search for novel peptides which can effectively interfere with E-cadherin interactions. Employing protein-protein and peptide-protein docking methods with varied levels of flexibility, we propose 115 different peptides with a high binding affinity for E-cadherin as candidates for disrupting the BBB. Several strongest binders have been selected for experimental validation and further sequence optimization. Additionally, conformations of selected peptides in aqueous solution were explored with molecular dynamics simulations, showing a general preference for extended structures and fast conformational equilibria, on the 10-100 ns time scales.  Thus, this work presents a systematic computational approach for generating novel peptides with high potential for disrupting the BBB and enabling drug delivery to the central nervous system.

A graphical abstract is attached.

We warmly welcome everyone to attend the talk and the Soft Matter Coffee Break after the seminar, held in room 2.63 (2nd floor).

Maria Ekiel-Jeżewska
Maciej Lisicki
Piotr Szymczak
Panagiotis Theodorakis
Marek Trippenbach



--
Dr hab. Maciej Lisicki, prof. UW
Institute of Theoretical Physics | Faculty of Physics
University of Warsaw
softmatter.fuw.edu.pl <http://softmatter.fuw.edu.pl/>
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