Targeting neuroblastoma cell surface proteins: Recommendations for homology modeling of hNET, ALK, and TrkB

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F17%3A43911479" target="_blank" >RIV/62156489:43210/17:43911479 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216305:26620/17:PU123080

Výsledek na webu

<a href="https://doi.org/10.3389/fnmol.2017.00007" target="_blank" >https://doi.org/10.3389/fnmol.2017.00007</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fnmol.2017.00007" target="_blank" >10.3389/fnmol.2017.00007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Targeting neuroblastoma cell surface proteins: Recommendations for homology modeling of hNET, ALK, and TrkB

Popis výsledku v původním jazyce

Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of &quot;good modeling practice&quot; to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.

Název v anglickém jazyce

Targeting neuroblastoma cell surface proteins: Recommendations for homology modeling of hNET, ALK, and TrkB

Popis výsledku anglicky

Targeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of &quot;good modeling practice&quot; to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

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

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Molecular Neuroscience

ISSN

1662-5099

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

20 January

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

7

Strana od-do

—

Kód UT WoS článku

000392250800001

EID výsledku v databázi Scopus

2-s2.0-85011003017