DFT, Molecular Docking, and Molecular Dynamics Analysis of Electronic Structure, Reactivity, and PTP1B Binding of Phenylacetic and Benzylmalonic Acid-Functionalized C60 Derivatives
- 1Universidad de Guadalajara, Centro Universitario de los Lagos, Departamento de Ciencias Exactas y Tecnología, Av. Enrique Díaz de León 1144, Lagos de Moreno 47460, Jalisco, Mexico
Abstract
Water-soluble C60 derivatives functionalized with phenylacetic acid (PhAA) and benzylmalonic acid (BnMA), together with their di- and tetrahydroxylated derivatives, were investigated using density functional theory, molecular docking, and molecular dynamics simulations to evaluate their electronic structure, local and global reactivity, and interactions with protein tyrosine phosphatase 1B (PTP1B). Successive hydroxylation steps were thermodynamically favorable, while electronic structure and reactivity analyses indicated that the fullerene cage retains features compatible with further ROS-related reactivity after hydroxylation. Electrostatic potential analysis revealed differentiated polarity between the fullerene and functionalization regions. Docking showed functionalization-dependent binding modes: PhAA-derived systems sampled both peripheral regions near the WPD and R loops and the catalytic pocket, whereas BnMA-derived systems consistently occupied the catalytic site and interacted with key residues, including Cys215 and Arg221. Molecular dynamics showed reduced flexibility in functionally relevant regions, reorganization of correlated motions, and average catalytic-pocket conformations that were more open than in apo-PTP1B. Overall, these results support the potential of these derivatives for ROS-related reactivity and modulation of PTP1B, although experimental validation is required to establish their biological activity.
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BibTeX
@article{rodriguezcelestino2026molecular,
title = {{DFT, Molecular Docking, and Molecular Dynamics Analysis of Electronic Structure, Reactivity, and PTP1B Binding of Phenylacetic and Benzylmalonic Acid-Functionalized C60 Derivatives}},
author = {Verónica Rodríguez-Celestino and Zuriel Natanael Cisneros-García and Jaime Gustavo Rodríguez-Zavala and Carlos Iván Méndez-Barrientos and José Guadalupe Facio-Muñoz},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31193543},
url = {https://www.mdpi.com/1420-3049/31/19/3543},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DFT, Molecular Docking, and Molecular Dynamics Analysis of Electronic Structure, Reactivity, and PTP1B Binding of Phenylacetic and Benzylmalonic Acid-Functionalized C60 Derivatives
AU - Verónica Rodríguez-Celestino
AU - Zuriel Natanael Cisneros-García
AU - Jaime Gustavo Rodríguez-Zavala
AU - Carlos Iván Méndez-Barrientos
AU - José Guadalupe Facio-Muñoz
PY - 2026
DA - 2026/10/04
JO - Molecules
DO - 10.3390/molecules31193543
UR - https://www.mdpi.com/1420-3049/31/19/3543
AB - Water-soluble C60 derivatives functionalized with phenylacetic acid (PhAA) and benzylmalonic acid (BnMA), together with their di- and tetrahydroxylated derivatives, were investigated using density functional theory, molecular docking, and molecular dynamics simulations to evaluate their electronic structure, local and global reactivity, and interactions with protein tyrosine phosphatase 1B (PTP1B). Successive hydroxylation steps were thermodynamically favorable, while electronic structure and reactivity analyses indicated that the fullerene cage retains features compatible with further ROS-related reactivity after hydroxylation. Electrostatic potential analysis revealed differentiated polarity between the fullerene and functionalization regions. Docking showed functionalization-dependent binding modes: PhAA-derived systems sampled both peripheral regions near the WPD and R loops and the catalytic pocket, whereas BnMA-derived systems consistently occupied the catalytic site and interacted with key residues, including Cys215 and Arg221. Molecular dynamics showed reduced flexibility in functionally relevant regions, reorganization of correlated motions, and average catalytic-pocket conformations that were more open than in apo-PTP1B. Overall, these results support the potential of these derivatives for ROS-related reactivity and modulation of PTP1B, although experimental validation is required to establish their biological activity.
SN - 1420-3049
ER -