Solvent Accessibility Promotes Rotamer Errors during Protein Modeling with Major Side-Chain Prediction Programs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F23%3A43923750" target="_blank" >RIV/62156489:43210/23:43923750 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jcim.3c00134" target="_blank" >https://doi.org/10.1021/acs.jcim.3c00134</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.3c00134" target="_blank" >10.1021/acs.jcim.3c00134</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Solvent Accessibility Promotes Rotamer Errors during Protein Modeling with Major Side-Chain Prediction Programs

Popis výsledku v původním jazyce

Side-chain rotamer prediction is one of the most critical late stages in protein 3D structure building. Highly advanced and specialized algorithms (e.g., FASPR, RASP, SCWRL4, and SCWRL4v) optimize this process by use of rotamer libraries, combinatorial searches, and scoring functions. We seek to identify the sources of key rotamer errors as a basis for correcting and improving the accuracy of protein modeling going forward. In order to evaluate the aforementioned programs, we process 2496 high-quality single-chained all-atom filtered 30% homology protein 3D structures and use discretized rotamer analysis to compare original with calculated structures. Among 513,024 filtered residue records, increased amino acid residue-dependent rotamer errors─associated in particular with polar and charged amino acid residues (ARG, LYS, and GLN)─clearly correlate with increased amino acid residue solvent accessibility and an increased residue tendency toward the adoption of non-canonical off rotamers which modeling programs struggle to predict accurately. Understanding the impact of solvent accessibility now appears key to improved side-chain prediction accuracies.

Název v anglickém jazyce

Solvent Accessibility Promotes Rotamer Errors during Protein Modeling with Major Side-Chain Prediction Programs

Popis výsledku anglicky

Side-chain rotamer prediction is one of the most critical late stages in protein 3D structure building. Highly advanced and specialized algorithms (e.g., FASPR, RASP, SCWRL4, and SCWRL4v) optimize this process by use of rotamer libraries, combinatorial searches, and scoring functions. We seek to identify the sources of key rotamer errors as a basis for correcting and improving the accuracy of protein modeling going forward. In order to evaluate the aforementioned programs, we process 2496 high-quality single-chained all-atom filtered 30% homology protein 3D structures and use discretized rotamer analysis to compare original with calculated structures. Among 513,024 filtered residue records, increased amino acid residue-dependent rotamer errors─associated in particular with polar and charged amino acid residues (ARG, LYS, and GLN)─clearly correlate with increased amino acid residue solvent accessibility and an increased residue tendency toward the adoption of non-canonical off rotamers which modeling programs struggle to predict accurately. Understanding the impact of solvent accessibility now appears key to improved side-chain prediction accuracies.

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

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Svazek periodika

63

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

4405-4422

Kód UT WoS článku

001023558400001

EID výsledku v databázi Scopus

2-s2.0-85164817104