End-Point Affinity Estimation of Galectin Ligands by Classical and Semiempirical Quantum Mechanical Potentials

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00605067" target="_blank" >RIV/61388963:_____/25:00605067 - isvavai.cz</a>

Alternative codes found

RIV/60461373:22330/25:43932710

Result on the web

<a href="https://doi.org/10.1021/acs.jcim.4c01659" target="_blank" >https://doi.org/10.1021/acs.jcim.4c01659</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.4c01659" target="_blank" >10.1021/acs.jcim.4c01659</a>

Result language

angličtina

Original language name

End-Point Affinity Estimation of Galectin Ligands by Classical and Semiempirical Quantum Mechanical Potentials

Original language description

The use of quantum mechanical potentials in protein-ligand affinity prediction is becoming increasingly feasible with growing computational power. To move forward, validation of such potentials on real-world challenges is necessary. To this end, we have collated an extensive set of over a thousand galectin inhibitors with known affinities and docked them into galectin-3. The docked poses were then used to systematically evaluate several modern force fields and semiempirical quantum mechanical (SQM) methods up to the tight-binding level under consistent computational workflow. Implicit solvation models available with the tested methods were used to simulate solvation effects. Overall, the best methods in this study achieved a Pearson correlation of 0.7-0.8 between the computed and experimental affinities. There were differences between the tested methods in their ability to rank ligands across the entire ligand set as well as within subsets of structurally similar ligands. A major discrepancy was observed for a subset of ligands that bind to the protein via a halogen bond, which was clearly challenging for all the tested methods. The inclusion of an entropic term calculated by the rigid-rotor-harmonic-oscillator approximation at SQM level slightly worsened correlation with experiment but brought the calculated affinities closer to experimental values. We also found that the success of the prediction strongly depended on the solvation model. Furthermore, we provide an in-depth analysis of the individual energy terms and their effect on the overall prediction accuracy.

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/GA22-17586S" target="_blank" >GA22-17586S: 15N isotopic labeling in NMR structural analysis of N-disaccharides</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Volume of the periodical

65

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

762-777

UT code for WoS article

001390015200001

EID of the result in the Scopus database

2-s2.0-85216280091