Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00559713" target="_blank" >RIV/61388963:_____/22:00559713 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/22:00128476 RIV/00216208:11310/22:10458346

Výsledek na webu

<a href="https://doi.org/10.1002/prot.26398" target="_blank" >https://doi.org/10.1002/prot.26398</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/prot.26398" target="_blank" >10.1002/prot.26398</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark

Popis výsledku v původním jazyce

Proteins are naturally formed by domains edging their functional and structural properties. A domain out of the context of an entire protein can retain its structure and to some extent also function on its own. These properties rationalize construction of artificial fusion multidomain proteins with unique combination of various functions. Information on the specific functional and structural characteristics of individual domains in the context of new artificial fusion proteins is inevitably encoded in sequential order of composing domains defining their mutual spatial positions. So the challenges in designing new proteins with new domain combinations lie dominantly in structure/function prediction and its context dependency. Despite the enormous body of publications on artificial fusion proteins, the task of their structure/function prediction is complex and nontrivial. The degree of spatial freedom facilitated by a linker between domains and their mutual orientation driven by noncovalent interactions is beyond a simple and straightforward methodology to predict their structure with reasonable accuracy. In the presented manuscript, we tested methodology using available modeling tools and computational methods. We show that the process and methodology of such prediction are not straightforward and must be done with care even when recently introduced AlphaFold II is used. We also addressed a question of benchmarking standards for prediction of multidomain protein structures-x-ray or Nuclear Magnetic Resonance experiments. On the study of six two-domain protein chimeras as well as their composing domains and their x-ray structures selected from PDB, we conclude that the major obstacle for justified prediction is inappropriate sampling of the conformational space by the explored methods. On the other hands, we can still address particular steps of the methodology and improve the process of chimera proteins prediction.

Název v anglickém jazyce

Fusion of two unrelated protein domains in a chimera protein and its 3D prediction: Justification of the x-ray reference structures as a prediction benchmark

Popis výsledku anglicky

Proteins are naturally formed by domains edging their functional and structural properties. A domain out of the context of an entire protein can retain its structure and to some extent also function on its own. These properties rationalize construction of artificial fusion multidomain proteins with unique combination of various functions. Information on the specific functional and structural characteristics of individual domains in the context of new artificial fusion proteins is inevitably encoded in sequential order of composing domains defining their mutual spatial positions. So the challenges in designing new proteins with new domain combinations lie dominantly in structure/function prediction and its context dependency. Despite the enormous body of publications on artificial fusion proteins, the task of their structure/function prediction is complex and nontrivial. The degree of spatial freedom facilitated by a linker between domains and their mutual orientation driven by noncovalent interactions is beyond a simple and straightforward methodology to predict their structure with reasonable accuracy. In the presented manuscript, we tested methodology using available modeling tools and computational methods. We show that the process and methodology of such prediction are not straightforward and must be done with care even when recently introduced AlphaFold II is used. We also addressed a question of benchmarking standards for prediction of multidomain protein structures-x-ray or Nuclear Magnetic Resonance experiments. On the study of six two-domain protein chimeras as well as their composing domains and their x-ray structures selected from PDB, we conclude that the major obstacle for justified prediction is inappropriate sampling of the conformational space by the explored methods. On the other hands, we can still address particular steps of the methodology and improve the process of chimera proteins prediction.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular 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

2022

Kód důvěrnosti údajů

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

Název periodika

Proteins-Structure, Function and Bioinformatics

ISSN

0887-3585

e-ISSN

1097-0134

Svazek periodika

90

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2067-2079

Kód UT WoS článku

000830348600001

EID výsledku v databázi Scopus

2-s2.0-85134755683