Selecting Collective Variables and Free Energy Methods for
Peptide Translocation Across Membranes.

J 2021

Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes.

KABELKA, Ivo, Radim BROŽEK a Robert VÁCHA

Základní údaje

Originální název

Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes.

Autoři

KABELKA, Ivo (203 Česká republika, domácí), Radim BROŽEK (203 Česká republika, domácí) a Robert VÁCHA (203 Česká republika, garant, domácí)

Vydání

Journal of Chemical Information and Modeling, USA, 2021, 1549-9596

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30107 Medicinal chemistry

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.162

Kód RIV

RIV/00216224:14740/21:00118991

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1021/acs.jcim.0c01312

UT WoS

000621663600025

Klíčová slova anglicky

Cell Membrane; Entropy; Molecular Dynamics Simulation; Peptides

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 4. 2022 08:15, Mgr. Michal Petr

Anotace

V originále

The selective permeability of cellular membranes is a crucial property for controlled transport into and out of cells. Molecules that can bypass the cellular machinery and spontaneously translocate across membranes could be used as therapeutics or drug carriers. Peptides are a prominent class of such molecules, which include natural and man-developed antimicrobial and cell-penetrating peptides. However, the necessary peptide properties for translocation remain elusive. Computer simulations could uncover these properties once we have a good collective variable (CV) that accurately describes the translocation process. Here, we developed a new CV, which includes a description of peptide insertion, local membrane deformation, and peptide internal degrees of freedom related to its charged groups. By comparison of CVs, we demonstrated that all these components are necessary for an accurate description of peptide translocation. Moreover, the advantages and disadvantages of three common methods for free-energy calculations with our CV were evaluated using the MARTINI coarse-grained model: umbrella sampling, umbrella sampling with replica exchange, and metadynamics. The developed CV leads to the reliable and effective calculation of the free energy of peptide translocation, and thus, it could be useful in the design of spontaneously translocating peptides.

Návaznosti

GA17-11571S, projekt VaV

Název: Amfifilní peptidy na fosfolipidových membránách

Investor: Grantová agentura ČR, Amphiphilic Peptides at Phospholipid Membranes

GA20-20152S, projekt VaV

Název: Proteinová přitažlivost a selektivita pro buněčné membrány

Investor: Grantová agentura ČR, Protein Affinity and Selectivity to Cellular Membranes

LL2007, projekt VaV

Název: Peptidoví zabijáci bakterií (Akronym: PeptideKillers)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Peptide Killers of Bacteria

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

90070, velká výzkumná infrastruktura

Název: IT4Innovations

Citovat

KABELKA, Ivo, Radim BROŽEK a Robert VÁCHA. Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes. Journal of Chemical Information and Modeling. USA, 2021, roč. 61, č. 2, s. 819-830. ISSN 1549-9596. Dostupné z: https://dx.doi.org/10.1021/acs.jcim.0c01312.

@article{1773098,
   author = {Kabelka, Ivo and Brožek, Radim and Vácha, Robert},
   article_location = {USA},
   article_number = {2},
   doi = {http://dx.doi.org/10.1021/acs.jcim.0c01312},
   keywords = {Cell Membrane; Entropy; Molecular Dynamics Simulation; Peptides},
   language = {eng},
   issn = {1549-9596},
   journal = {Journal of Chemical Information and Modeling},
   title = {Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes.},
   url = {https://pubs.acs.org/doi/10.1021/acs.jcim.0c01312},
   volume = {61},
   year = {2021}
}

TY  - JOUR
ID  - 1773098
AU  - Kabelka, Ivo - Brožek, Radim - Vácha, Robert
PY  - 2021
TI  - Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes.
JF  - Journal of Chemical Information and Modeling
VL  - 61
IS  - 2
SP  - 819-830
EP  - 819-830
SN  - 15499596
KW  - Cell Membrane
KW  - Entropy
KW  - Molecular Dynamics Simulation
KW  - Peptides
UR  - https://pubs.acs.org/doi/10.1021/acs.jcim.0c01312
N2  - The selective permeability of cellular membranes is a crucial property for controlled transport into and out of cells. Molecules that can bypass the cellular machinery and spontaneously translocate across membranes could be used as therapeutics or drug carriers. Peptides are a prominent class of such molecules, which include natural and man-developed antimicrobial and cell-penetrating peptides. However, the necessary peptide properties for translocation remain elusive. Computer simulations could uncover these properties once we have a good collective variable (CV) that accurately describes the translocation process. Here, we developed a new CV, which includes a description of peptide insertion, local membrane deformation, and peptide internal degrees of freedom related to its charged groups. By comparison of CVs, we demonstrated that all these components are necessary for an accurate description of peptide translocation. Moreover, the advantages and disadvantages of three common methods for free-energy calculations with our CV were evaluated using the MARTINI coarse-grained model: umbrella sampling, umbrella sampling with replica exchange, and metadynamics. The developed CV leads to the reliable and effective calculation of the free energy of peptide translocation, and thus, it could be useful in the design of spontaneously translocating peptides.
ER  -

KABELKA, Ivo, Radim BROŽEK a Robert VÁCHA. Selecting Collective Variables and Free Energy Methods for Peptide Translocation Across Membranes. \textit{Journal of Chemical Information and Modeling}. USA, 2021, roč.~61, č.~2, s.~819-830. ISSN~1549-9596. Dostupné z: https://dx.doi.org/10.1021/acs.jcim.0c01312.

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