Reconstructing the Free Energy Profiles Describing the Switching Mechanism of a pH-Dependent DNA Nanodevice from ABMD Simulations
| Autor: | Alessandro Desideri, Mattia Falconi, Alice Romeo, Federico Iacovelli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Technology
Materials science QH301-705.5 QC1-999 Protonation 02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Molecular dynamics DNA triple helix General Materials Science Biology (General) DNA nanoswitch QD1-999 Instrumentation Nanodevice Fluid Flow and Transfer Processes ABMD simulations Settore BIO/11 Oligonucleotide Physics Process Chemistry and Technology General Engineering Engineering (General). Civil engineering (General) 021001 nanoscience & nanotechnology Diprotic acid free energy profiles 0104 chemical sciences Computer Science Applications Chemistry chemistry Chemical physics Helix TA1-2040 0210 nano-technology Linker DNA |
| Zdroj: | Applied Sciences Volume 11 Issue 9 Applied Sciences, Vol 11, Iss 4052, p 4052 (2021) |
| ISSN: | 2076-3417 |
| DOI: | 10.3390/app11094052 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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