Toward Ab Initio Protein Folding: Inherent Secondary Structure Propensity of Short Peptides from the Bioinformatics and Quantum-Chemical Perspective

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00502462" target="_blank" >RIV/61388963:_____/19:00502462 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.8b09245" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.8b09245</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.8b09245" target="_blank" >10.1021/acs.jpcb.8b09245</a>

Result language

angličtina

Original language name

Toward Ab Initio Protein Folding: Inherent Secondary Structure Propensity of Short Peptides from the Bioinformatics and Quantum-Chemical Perspective

Original language description

By combining bioinformatics with quantum-chemical calculations, we attempt to address quantitatively some of the physical principles underlying protein folding. The former allowed us to identify tripeptide sequences in existing protein three-dimensional structures with a strong preference for either helical or extended structure. The selected representatives of pro-helical and pro-extended sequences were converted into “isolated” tripeptides-capped at N- and C-termini-and these were subjected to an extensive conformational sampling and geometry optimization (typically thousands to tens of thousands of conformers for each tripeptide). For each conformer, the QM(DFT-D3)/COSMO-RS free-energy value was then calculated, G(conf)(solv). The Delta G(conf)(solv) is expected to provide an objective, unbiased, and quantitatively accurate measure of the conformational preference of the particular tripeptide sequence. It has been shown that irrespective of the helical vs extended preferences of the selected tripeptide sequences in context of the protein, most of the low-energy conformers of isolated tripeptides prefer the R-helical structure. Nevertheless, pro-helical tripeptides show slightly stronger helix preference than their pro-extended counterparts. Furthermore, when the sampling is repeated in the presence of a partner tripeptide to mimic the situation in a beta-sheet, pro-extended tripeptides (exemplified by the VIV) show a larger free-energy benefit than pro-helical tripeptides (exemplified by the EAM). This effect is even more pronounced in a hydrophobic solvent, which mimics the less polar parts of a protein. This is in line with our bioinformatic results showing that the majority of pro-extended tripeptides are hydrophobic. The preference for a specific secondary structure by the studied tripeptides is thus governed by the plasticity to adopt to its environment. In addition, we show that most of the “naturally occurring” conformations of tripeptide sequences, i.e., those found in existing three-dimensional protein structures, are within similar to 10 kcal.mol(-1) from their global minima. In summary, our “ab initio” data suggest that complex protein structures may start to emerge already at the level of their small oligopeptidic units, which is in line with a hierarchical nature of protein folding.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GA17-24155S" target="_blank" >GA17-24155S: Exploring Conformational Space of Short Peptides by Advanced Quantum Chemical and Solvation Methods: A Key to Understand Protein Structures?</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Volume of the periodical

123

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

1215-1227

UT code for WoS article

000459223800001

EID of the result in the Scopus database

2-s2.0-85061262398