An MD View of Ligand Binding

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F25%3A00643899" target="_blank" >RIV/61388971:_____/25:00643899 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/30/24/4678" target="_blank" >https://www.mdpi.com/1420-3049/30/24/4678</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules30244678" target="_blank" >10.3390/molecules30244678</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An MD View of Ligand Binding

Popis výsledku v původním jazyce

Protein-ligand complexes in crystal structures are well described by an array of bonding interactions among precisely defined functional groups. The present work examines how one representative complex behaves in one-microsecond molecular dynamics simulations, starting from a crystal structure with a native biological ligand bound, and proceeding to simulations of structures derived by docking of that native ligand, and then to docking of selected ligand analogs. The MD behaviors and system energies calculated in RMSD plateau regions using MM/GBSA are similar when initiated from the crystal structure or the structure with the docked native ligand, although independent replicate simulations differ. Despite these similarities, interatomic contact frequencies indicate that some contacts observed in the crystal structure are rarely sampled again, others are sampled only intermittently, and new contacts are recruited that can be more persistent. Docked structures of non-native ligand analogs were chosen for simulation by screening manually for features consistent with known binding interactions, and these displayed behaviors similar to those for the native ligand and, in some cases, similar calculated energies. Overall, ligands appear to cooperate dynamically with the protein in forming the observed interactions.

Název v anglickém jazyce

An MD View of Ligand Binding

Popis výsledku anglicky

Protein-ligand complexes in crystal structures are well described by an array of bonding interactions among precisely defined functional groups. The present work examines how one representative complex behaves in one-microsecond molecular dynamics simulations, starting from a crystal structure with a native biological ligand bound, and proceeding to simulations of structures derived by docking of that native ligand, and then to docking of selected ligand analogs. The MD behaviors and system energies calculated in RMSD plateau regions using MM/GBSA are similar when initiated from the crystal structure or the structure with the docked native ligand, although independent replicate simulations differ. Despite these similarities, interatomic contact frequencies indicate that some contacts observed in the crystal structure are rarely sampled again, others are sampled only intermittently, and new contacts are recruited that can be more persistent. Docked structures of non-native ligand analogs were chosen for simulation by screening manually for features consistent with known binding interactions, and these displayed behaviors similar to those for the native ligand and, in some cases, similar calculated energies. Overall, ligands appear to cooperate dynamically with the protein in forming the observed interactions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

1420-3049

Svazek periodika

30

Číslo periodika v rámci svazku

24

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

43

Strana od-do

4678

Kód UT WoS článku

001647067400001

EID výsledku v databázi Scopus

2-s2.0-105025753415