Mapping Conformational Space of All 8000 Tripeptides by Quantum Chemical Methods: What Strain Is Affordable within Folded Protein Chains?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00542023" target="_blank" >RIV/61388963:_____/21:00542023 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1021/acs.jpcb.0c09251" target="_blank" >https://doi.org/10.1021/acs.jpcb.0c09251</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.0c09251" target="_blank" >10.1021/acs.jpcb.0c09251</a>

Result language

angličtina

Original language name

Mapping Conformational Space of All 8000 Tripeptides by Quantum Chemical Methods: What Strain Is Affordable within Folded Protein Chains?

Original language description

To gain more insight into the physicochemical aspects of a protein structure from the first principles, conformational space of all 8000 “capped” tripeptides (i.e., N-Ac-X1X2X3-NH-CH3, where Xi is one of the 20 natural amino acids) was investigated computationally. An enormous dataset (denoted P-CONF_1.6M and containing close to 1 600 000 conformers in total) has been obtained by employing a composite protocol combining density functional theory, semiempirical quantum mechanics (SQM), and state-of-the-art solvation methods with 1000 K molecular dynamics (MD) used to generate initial structures (200 snapshots for each tripeptide). This allowed us to present the first rigorous QM-based glimpse at the vast conformational space spanned by small protein fragments. The same computational procedure was repeated for tripeptide fragments taken from the SCOPe database of three-dimensional protein folds, by restraining them to their geometry in a protein. Such complementary data allowed us to compare the distribution of conformational strain energies of unrestrained tripeptidic fragments “in solvent” with those in existing protein chains. Besides providing a rigorous (ab initio) proof of a few well-known concepts and hypotheses concerning protein structures, such as the distribution of (φ, ψ) angles in Ramachandran plots, we have made several observations that came as a certain surprise: (1) distribution of conformational energies does not significantly differ between the “unbiased/unrestrained” conformers obtained from MD sampling in solvent and the biased conformers, i.e., those of a given tripeptide obtained from protein structures, (2) conformational (strain) energy window up to ∼20 to 25 kcal·mol–1 is readily available to tripeptide fragments within the context of a protein chain, (3) overpopulation in certain regions of Ramachandran plot was observed for the unbiased conformers. Last but not least, the massive dataset of accurate (DFT-D3//COSMO-RS) conformational (free) energies of ∼1.6 M peptide conformers, P-CONF_1.6M, obtained throughout this work may serve as excellent dataset for calibrating and benchmarking of popular force fields.

Czech name

—

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/GA20-08772S" target="_blank" >GA20-08772S: Fundamental Principles of Protein Folding and Protein-Ligand Interactions Revealed by High-Level Quantum Chemical Calculations</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

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

1520-5207

Volume of the periodical

125

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

58-69

UT code for WoS article

000661200000007

EID of the result in the Scopus database

2-s2.0-85099629888