Cargando…
Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method
The search for efficient inhibitors targeting Aβ oligomers and fibrils is an important issue in Alzheimer's disease treatment. As a consequence, an accurate and computationally cheap approach to estimate the binding affinity for many ligands interacting with Aβ peptides is very important. Here,...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063661/ https://www.ncbi.nlm.nih.gov/pubmed/35515829 http://dx.doi.org/10.1039/c9ra01177c |
_version_ | 1784699211166515200 |
---|---|
author | Ngo, Son Tung Mai, Binh Khanh Derreumaux, Philippe Vu, Van V. |
author_facet | Ngo, Son Tung Mai, Binh Khanh Derreumaux, Philippe Vu, Van V. |
author_sort | Ngo, Son Tung |
collection | PubMed |
description | The search for efficient inhibitors targeting Aβ oligomers and fibrils is an important issue in Alzheimer's disease treatment. As a consequence, an accurate and computationally cheap approach to estimate the binding affinity for many ligands interacting with Aβ peptides is very important. Here, the calculated binding free energies of 30 ligands interacting with 12Aβ(11–40) peptides using the linear interaction energy (LIE) approach are found to be in good correlation with experimental data (R = 0.79). The binding affinities of these complexes are also calculated by using free energy perturbation (FEP) and molecular mechanic/Poisson–Boltzmann surface area (MM/PBSA) methods. The time-consuming FEP method provides results with similar correlation (R = 0.72), whereas MM/PBSA calculations show very low correlation with experimental data (R = 0.27). In all complexes, van der Waals interactions contribute much more than electrostatic interactions. The LIE model, which is much less time-consuming than both the FEP and MM/PBSA methods, opens the door to accurate and rapid affinity prediction of ligands with Aβ peptides and the design of new ligands. |
format | Online Article Text |
id | pubmed-9063661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90636612022-05-04 Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method Ngo, Son Tung Mai, Binh Khanh Derreumaux, Philippe Vu, Van V. RSC Adv Chemistry The search for efficient inhibitors targeting Aβ oligomers and fibrils is an important issue in Alzheimer's disease treatment. As a consequence, an accurate and computationally cheap approach to estimate the binding affinity for many ligands interacting with Aβ peptides is very important. Here, the calculated binding free energies of 30 ligands interacting with 12Aβ(11–40) peptides using the linear interaction energy (LIE) approach are found to be in good correlation with experimental data (R = 0.79). The binding affinities of these complexes are also calculated by using free energy perturbation (FEP) and molecular mechanic/Poisson–Boltzmann surface area (MM/PBSA) methods. The time-consuming FEP method provides results with similar correlation (R = 0.72), whereas MM/PBSA calculations show very low correlation with experimental data (R = 0.27). In all complexes, van der Waals interactions contribute much more than electrostatic interactions. The LIE model, which is much less time-consuming than both the FEP and MM/PBSA methods, opens the door to accurate and rapid affinity prediction of ligands with Aβ peptides and the design of new ligands. The Royal Society of Chemistry 2019-04-23 /pmc/articles/PMC9063661/ /pubmed/35515829 http://dx.doi.org/10.1039/c9ra01177c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Ngo, Son Tung Mai, Binh Khanh Derreumaux, Philippe Vu, Van V. Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title | Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title_full | Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title_fullStr | Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title_full_unstemmed | Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title_short | Adequate prediction for inhibitor affinity of Aβ(40) protofibril using the linear interaction energy method |
title_sort | adequate prediction for inhibitor affinity of aβ(40) protofibril using the linear interaction energy method |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063661/ https://www.ncbi.nlm.nih.gov/pubmed/35515829 http://dx.doi.org/10.1039/c9ra01177c |
work_keys_str_mv | AT ngosontung adequatepredictionforinhibitoraffinityofab40protofibrilusingthelinearinteractionenergymethod AT maibinhkhanh adequatepredictionforinhibitoraffinityofab40protofibrilusingthelinearinteractionenergymethod AT derreumauxphilippe adequatepredictionforinhibitoraffinityofab40protofibrilusingthelinearinteractionenergymethod AT vuvanv adequatepredictionforinhibitoraffinityofab40protofibrilusingthelinearinteractionenergymethod |