Accuracy and precision of binding free energy prediction for a tacrine related lead inhibitor of acetylcholinesterase with an arsenal of supercomputerized molecular modelling methods: a comparative study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50018391" target="_blank" >RIV/62690094:18470/22:50018391 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/22:10452311

Result on the web

<a href="https://www.tandfonline.com/doi/abs/10.1080/07391102.2021.1957716?journalCode=tbsd20" target="_blank" >https://www.tandfonline.com/doi/abs/10.1080/07391102.2021.1957716?journalCode=tbsd20</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2021.1957716" target="_blank" >10.1080/07391102.2021.1957716</a>

Result language

angličtina

Original language name

Accuracy and precision of binding free energy prediction for a tacrine related lead inhibitor of acetylcholinesterase with an arsenal of supercomputerized molecular modelling methods: a comparative study

Original language description

Nowadays, advanced computational chemistry methods offer various strategies for revealing prospective hit structures in drug development essentially through accurate binding free energy predictions. After the era of molecular docking and quantitative structure-activity relationships, much interest has been lately oriented to perturbed molecular dynamic approaches like replica exchange with solute tempering and free energy perturbation (REST/FEP) and the potential of the mean force with adaptive biasing and accelerated weight histograms (PMF/AWH). Both of these receptor-based techniques can exploit exascale CPU&amp;GPU supercomputers to achieve high throughput performance. In this fundamental study, we have compared the predictive power of a panel of supercomputerized molecular modelling methods to distinguish the major binding modes and the corresponding binding free energies of a promising tacrine related potential antialzheimerics in human acetylcholinesterase. The binding free energies were estimated using flexible molecular docking, molecular mechanics/generalized Born surface area/Poisson-Boltzmann surface area (MM/GBSA/PBSA), transmutation REST/FEP with 12 x 5 ns/lambda windows, annihilation FEP with 20 x 5 ns/lambda steps, PMF with weight histogram analysis method (WHAM) and 40 x 5 ns samples, and PMF/AWH with 10 x 100 ns replicas. Confrontation of the classical approaches such as canonical molecular dynamics and molecular docking with alchemical calculations and steered molecular dynamics enabled us to show how large errors in Delta G predictions can be expected if these in silico methods are employed in the elucidation of a common case of enzyme inhibition.

Czech name

—

Czech description

—

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/EF18_069%2F0010054" target="_blank" >EF18_069/0010054: IT4Neuro(degeneration)</a><br>

Continuities

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

Publication year

2022

Confidentiality

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

Name of the periodical

Journal of biomolecular structure and dynamics

ISSN

0739-1102

e-ISSN

1538-0254

Volume of the periodical

40

Issue of the periodical within the volume

21

Country of publishing house

US - UNITED STATES

Number of pages

29

Pages from-to

11291-11319

UT code for WoS article

000679222700001

EID of the result in the Scopus database

2-s2.0-85111639049