Multiple factors modulating the formation of toroidal membrane pores

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F23%3A00132221" target="_blank" >RIV/00216224:14740/23:00132221 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Multiple factors modulating the formation of toroidal membrane pores

Popis výsledku v původním jazyce

Pore formation and stability in cell membranes play a pivotal role in drug delivery into cells such as bacteria1. Particularly, the stability of toroidal pores — pores with a doughnut-shaped geometry where lipid headgroups cover the pore rim — is primarily regulated by the rim-associated line tension. While molecular simulations are a known tool for screening drug candidates, they can also forecast the potential of new therapeutics to modulate line tension. However, not all models (known as force fields) tailored for biological computer simulations accurately capture the line tension of lipid membrane compositions characteristic of mammalian and bacterial cells. This deficiency eventually hinders the drug design. In this work, we investigate the use of molecular dynamics simulations for the rational design of novel molecules, including antimicrobial peptides known to form pores and translocate across cell membranes3. We first delve into factors like lipid composition, which varies between mammalian and bacterial cells, and the unique solution environment, elaborating on their impact on the line tension. Furthermore, we describe the complete process of toroidal pore formation, its molecular origins, and showcase methods to assess the pore formation by computer simulations using available simulation models.

Název v anglickém jazyce

Multiple factors modulating the formation of toroidal membrane pores

Popis výsledku anglicky

Pore formation and stability in cell membranes play a pivotal role in drug delivery into cells such as bacteria1. Particularly, the stability of toroidal pores — pores with a doughnut-shaped geometry where lipid headgroups cover the pore rim — is primarily regulated by the rim-associated line tension. While molecular simulations are a known tool for screening drug candidates, they can also forecast the potential of new therapeutics to modulate line tension. However, not all models (known as force fields) tailored for biological computer simulations accurately capture the line tension of lipid membrane compositions characteristic of mammalian and bacterial cells. This deficiency eventually hinders the drug design. In this work, we investigate the use of molecular dynamics simulations for the rational design of novel molecules, including antimicrobial peptides known to form pores and translocate across cell membranes3. We first delve into factors like lipid composition, which varies between mammalian and bacterial cells, and the unique solution environment, elaborating on their impact on the line tension. Furthermore, we describe the complete process of toroidal pore formation, its molecular origins, and showcase methods to assess the pore formation by computer simulations using available simulation models.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10200 - Computer and information sciences

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů