Interplay between Conformational Strain and Intramolecular Interaction in Protein Structures: Which of Them Is Evolutionarily Conserved?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00524184" target="_blank" >RIV/61388963:_____/20:00524184 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.9b11784" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.9b11784</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.9b11784" target="_blank" >10.1021/acs.jpcb.9b11784</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interplay between Conformational Strain and Intramolecular Interaction in Protein Structures: Which of Them Is Evolutionarily Conserved?

Popis výsledku v původním jazyce

By computing strain energies of peptide fragments within protein structures and their intramolecular interaction energies, we attempt to reveal general biophysical trends behind the secondary structure formation in the context of protein evolution. Our “protein basis set” consisted of 1143 representatives of different folds obtained from curated SCOPe database, and for each member of the set, the strain and intramolecular energy was calculated on the “rolling tripeptide” basis, employing the DFT-D3/COSMO-RS method for the former and the QM-calibrated force field method (MM) for the latter. The calculated data, strain and interactions, were correlated with the conservation of amino acid residues in secondary structure elements and also with the level of the residue burial within the protein three-dimensional structure. It allowed us to formulate several observations concerning fundamental differences between two main secondary structure motifs: α-helices and β-strands. We have shown that a strong interaction is one of the determining characteristics of the β-sheet formation, at least at the level of tripeptides (and likely penta- or heptapeptides, too), and that the β-strand is a prevailing secondary structure in the strongly-interacting regions of the protein folds conserved by evolution. On the other hand, low strain was neither proven to be an important physicochemical property conserved by evolution nor does it correlate with the propensity for the α-helix and β-strand. Finally, it has been demonstrated that the strong interaction has a certain level of connection with residue burial, however, we demonstrate that these two characteristics should be rather regarded as two complementary factors. These findings represent an important contribution to understanding protein folding from first principles, which is a complementary approach to ongoing efforts to solve the protein folding problem by knowledge-based approaches and machine-learning.

Název v anglickém jazyce

Interplay between Conformational Strain and Intramolecular Interaction in Protein Structures: Which of Them Is Evolutionarily Conserved?

Popis výsledku anglicky

By computing strain energies of peptide fragments within protein structures and their intramolecular interaction energies, we attempt to reveal general biophysical trends behind the secondary structure formation in the context of protein evolution. Our “protein basis set” consisted of 1143 representatives of different folds obtained from curated SCOPe database, and for each member of the set, the strain and intramolecular energy was calculated on the “rolling tripeptide” basis, employing the DFT-D3/COSMO-RS method for the former and the QM-calibrated force field method (MM) for the latter. The calculated data, strain and interactions, were correlated with the conservation of amino acid residues in secondary structure elements and also with the level of the residue burial within the protein three-dimensional structure. It allowed us to formulate several observations concerning fundamental differences between two main secondary structure motifs: α-helices and β-strands. We have shown that a strong interaction is one of the determining characteristics of the β-sheet formation, at least at the level of tripeptides (and likely penta- or heptapeptides, too), and that the β-strand is a prevailing secondary structure in the strongly-interacting regions of the protein folds conserved by evolution. On the other hand, low strain was neither proven to be an important physicochemical property conserved by evolution nor does it correlate with the propensity for the α-helix and β-strand. Finally, it has been demonstrated that the strong interaction has a certain level of connection with residue burial, however, we demonstrate that these two characteristics should be rather regarded as two complementary factors. These findings represent an important contribution to understanding protein folding from first principles, which is a complementary approach to ongoing efforts to solve the protein folding problem by knowledge-based approaches and machine-learning.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA20-08772S" target="_blank" >GA20-08772S: Objevování základních principů struktury proteinů a protein-ligandových komplexů pokročilými metodami kvantové chemie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

124

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

3252-3260

Kód UT WoS článku

000529216600002

EID výsledku v databázi Scopus

2-s2.0-85084027819