AHoJ-DB: A PDB-wide Assignment of apo & holo Relationships Based on Individual Protein-Ligand Interactions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00585153" target="_blank" >RIV/61388963:_____/24:00585153 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11320/24:10487125 RIV/00216208:11310/24:10487125

Výsledek na webu

<a href="https://doi.org/10.1016/j.jmb.2024.168545" target="_blank" >https://doi.org/10.1016/j.jmb.2024.168545</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jmb.2024.168545" target="_blank" >10.1016/j.jmb.2024.168545</a>

Jazyk výsledku

angličtina

Název v původním jazyce

AHoJ-DB: A PDB-wide Assignment of apo & holo Relationships Based on Individual Protein-Ligand Interactions

Popis výsledku v původním jazyce

A single protein structure is rarely sufficient to capture the conformational variability of a protein. Both bound and unbound (holo and apo) forms of a protein are essential for understanding its geometry and making meaningful comparisons. Nevertheless, docking or drug design studies often still consider only single protein structures in their holo form, which are for the most part rigid. With the recent explosion in the field of structural biology, large, curated datasets are urgently needed. Here, we use a previously developed application (AHoJ) to perform a comprehensive search for apo-holo pairs for 468,293 biologically relevant protein-ligand interactions across 27,983 proteins. In each search, the binding pocket is captured and mapped across existing structures within the same UniProt, and the mapped pockets are annotated as apo or holo, based on the presence or absence of ligands. We assemble the results into a database, AHoJ-DB (www.apoholo.cz/db), that captures the variability of proteins with identical sequences, thereby exposing the agents responsible for the observed differences in geometry. We report several metrics for each annotated pocket, and we also include binding pockets that form at the interface of multiple chains. Analysis of the database shows that about 24% of the binding sites occur at the interface of two or more chains and that less than 50% of the total binding sites processed have an apo form in the PDB. These results can be used to train and evaluate predictors, discover potentially druggable proteins, and reveal protein- and ligand-specific relationships that were previously obscured by intermittent or partial data. Availability: www.apoholo.cz/db.

Název v anglickém jazyce

AHoJ-DB: A PDB-wide Assignment of apo & holo Relationships Based on Individual Protein-Ligand Interactions

Popis výsledku anglicky

A single protein structure is rarely sufficient to capture the conformational variability of a protein. Both bound and unbound (holo and apo) forms of a protein are essential for understanding its geometry and making meaningful comparisons. Nevertheless, docking or drug design studies often still consider only single protein structures in their holo form, which are for the most part rigid. With the recent explosion in the field of structural biology, large, curated datasets are urgently needed. Here, we use a previously developed application (AHoJ) to perform a comprehensive search for apo-holo pairs for 468,293 biologically relevant protein-ligand interactions across 27,983 proteins. In each search, the binding pocket is captured and mapped across existing structures within the same UniProt, and the mapped pockets are annotated as apo or holo, based on the presence or absence of ligands. We assemble the results into a database, AHoJ-DB (www.apoholo.cz/db), that captures the variability of proteins with identical sequences, thereby exposing the agents responsible for the observed differences in geometry. We report several metrics for each annotated pocket, and we also include binding pockets that form at the interface of multiple chains. Analysis of the database shows that about 24% of the binding sites occur at the interface of two or more chains and that less than 50% of the total binding sites processed have an apo form in the PDB. These results can be used to train and evaluate predictors, discover potentially druggable proteins, and reveal protein- and ligand-specific relationships that were previously obscured by intermittent or partial data. Availability: www.apoholo.cz/db.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Biology

ISSN

0022-2836

e-ISSN

1089-8638

Svazek periodika

436

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

168545

Kód UT WoS článku

001331535400001

EID výsledku v databázi Scopus

2-s2.0-85188992065