Featured ApplicationEnhanced sampling molecular dynamics simulation methods for the design and refinement of functional DNA nanodevices.The pH-responsive behavior of six triple-helix DNA nanoswitches, differing in the number of protonation centers (two or four) and in the length of the linker (5, 15 or 25 bases), connecting the double-helical region to the single-strand triplex-forming region, was characterized at the atomistic level through Adaptively Biased Molecular Dynamics simulations. The reconstruction of the free energy profiles of triplex-forming oligonucleotide unbinding from the double helix identified a different minimum energy path for the three diprotic nanoswitches, depending on the length of the connecting linker and leading to a different per-base unbinding profile. The same analyses carried out on the tetraprotic switches indicated that, in the presence of four protonation centers, the unbinding process occurs independently of the linker length. The simulation data provide an atomistic explanation for previously published experimental results showing, only in the diprotic switch, a two unit increase in the pKa switching mechanism decreasing the linker length from 25 to 5 bases, endorsing the validity of computational methods for the design and refinement of functional DNA nanodevices.

Romeo, A., Falconi, M., Desideri, A., Iacovelli, F. (2021). Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations. APPLIED SCIENCES, 11(9), 4052 [10.3390/app11094052].

Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations

Falconi, M;Desideri, A;Iacovelli, F
2021

Abstract

Featured ApplicationEnhanced sampling molecular dynamics simulation methods for the design and refinement of functional DNA nanodevices.The pH-responsive behavior of six triple-helix DNA nanoswitches, differing in the number of protonation centers (two or four) and in the length of the linker (5, 15 or 25 bases), connecting the double-helical region to the single-strand triplex-forming region, was characterized at the atomistic level through Adaptively Biased Molecular Dynamics simulations. The reconstruction of the free energy profiles of triplex-forming oligonucleotide unbinding from the double helix identified a different minimum energy path for the three diprotic nanoswitches, depending on the length of the connecting linker and leading to a different per-base unbinding profile. The same analyses carried out on the tetraprotic switches indicated that, in the presence of four protonation centers, the unbinding process occurs independently of the linker length. The simulation data provide an atomistic explanation for previously published experimental results showing, only in the diprotic switch, a two unit increase in the pKa switching mechanism decreasing the linker length from 25 to 5 bases, endorsing the validity of computational methods for the design and refinement of functional DNA nanodevices.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11
English
DNA nanoswitch
ABMD simulations
free energy profiles
DNA triple helix
Romeo, A., Falconi, M., Desideri, A., Iacovelli, F. (2021). Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations. APPLIED SCIENCES, 11(9), 4052 [10.3390/app11094052].
Romeo, A; Falconi, M; Desideri, A; Iacovelli, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/276527
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