| Autor: |
Ortiz de Luzuriaga I; CICnanoGUNE BRTA, Tolosa Hiribidea 76, E-20018, Donostia - San Sebastián, Spain. adria.gil.mestres@csic.es.; Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, Euskal Herriko Uniberstitatea, UPV/EHU, 20080 Donostia, Euskadi, Spain. xabier.lopez@ehu.es., Elleuchi S; Laboratoire de Chimie Inorganique, LR17ES07, Université de Sfax, Faculté de Sciences de Sfax, 3000 Sfax, Tunisia., Jarraya K; Laboratoire de Chimie Inorganique, LR17ES07, Université de Sfax, Faculté de Sciences de Sfax, 3000 Sfax, Tunisia., Artacho E; CICnanoGUNE BRTA, Tolosa Hiribidea 76, E-20018, Donostia - San Sebastián, Spain. adria.gil.mestres@csic.es.; Theory of Condensed Matter, Cavendish Laboratory, University of Cambridge, J. J. Thomson Ave., Cambridge CB3 0HE, UK.; Ikerbasque, Basque Foundation for Science, 48011 Bilbao, Spain.; Donostia International Physics Center, 20018 Donostia, Spain., López X; Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, Euskal Herriko Uniberstitatea, UPV/EHU, 20080 Donostia, Euskadi, Spain. xabier.lopez@ehu.es.; Donostia International Physics Center, 20018 Donostia, Spain., Gil A; CICnanoGUNE BRTA, Tolosa Hiribidea 76, E-20018, Donostia - San Sebastián, Spain. adria.gil.mestres@csic.es.; ARAID Foundation, Zaragoza, Spain.; Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH) CSIC - Universidad de Zaragoza, C/Pedro Cerbuna 12, 50009, Zaragoza, Spain.; BioISI - Biosystems and Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal. |
| Abstrakt: |
The computational study of DNA and its interaction with ligands is a highly relevant area of research, with significant consequences for developing new therapeutic strategies. However, the computational description of such large and complex systems requires considering interactions of different types simultaneously in a balanced way, such as non-covalent weak interactions (namely hydrogen bonds and stacking), metal-ligand interactions, polarisation and charge transfer effects. All these considerations imply a real challenge for computational chemistry. The possibility of studying large biological systems using quantum methods for the entire system requires significant computational resources, with improvements in parallelisation and optimisation of theoretical strategies. Computational methods, such as Linear-Scaling Density Functional Theory (LS-DFT) and DLPNO-CCSD(T), may allow performing ab initio quantum mechanics calculations, including the electronic structure for large biological systems, in a reasonable computing time. In this work, we study the interaction of small molecules and cations with DNA (both duplex DNA and G-quadruplexes), comparing different computational methods: a LS-DFT method at the LMKLL/DZDP level of theory, semi-empirical methods (PM6-DH2 and PM7), mixed QM/MM, and DLPNO-CCSD(T). Our goal is to demonstrate the adequacy of LS-DFT to treat the different types of interactions present in DNA-dependent systems. We show that LMKLL/DZDP using SIESTA can yield very accurate geometries and energetics in all the different systems considered in this work: duplex DNA (dDNA), phenanthroline intercalating dDNA, G-quadruplexes, and metal-G-tetrads considering alkaline metals of different sizes. As far as we know, this is the first time that full G-quadruplex geometry optimisations have been carried out using a DFT method thanks to its linear-scaling capabilities. Moreover, we show that LS-DFT provides high-quality structures, and some semi-empirical Hamiltonians can also yield suitable geometries. However, DLPNO-CCSD(T) and LS-DFT are the only methods that accurately describe interaction energies for all the systems considered in our study. |
