Structure and dynamics of proflavine association around DNA
| Autor: | Wilbee D. Sasikala, Arnab Mukherjee |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Molecular Structure
010304 chemical physics Intercalation (chemistry) Stacking General Physics and Astronomy DNA 010402 general chemistry 01 natural sciences Small molecule 0104 chemical sciences Kinetics chemistry.chemical_compound Molecular dynamics Crystallography Spectrometry Fluorescence chemistry 0103 physical sciences Bound state Molecule Physical and Theoretical Chemistry Dimerization Proflavine |
| Zdroj: | Physical Chemistry Chemical Physics. 18:10383-10391 |
| ISSN: | 1463-9084 1463-9076 |
| DOI: | 10.1039/c5cp07789c |
| Popis: | Proflavine is a small molecule that intercalates into DNA and, thereby, acts as an anticancer agent. Intercalation of proflavine is shown to be a two-step process in which the first step is believed to be the formation of a pre-intercalative outside bound state. Experimental studies so far have been unable to capture the nature of the outside bound state. However, the sub-millisecond timescale observed in fluorescence kinetic experiments is often attributed to the binding of proflavine outside of DNA. Here, we have performed molecular dynamics simulations with multiple proflavine molecules to study the structure and dynamics of the formation of the outside bound state of DNA at different ion concentrations. We observed that the timescale of the outside bound state formation is, at least, five orders of magnitude faster (in nanoseconds) than the experimentally reported timescale (sub-milliseconds) attributed to binding outside DNA. Moreover, we also observed the stacked arrangement of proflavine all around DNA, which is different from the experimentally predicted stacking arrangement perpendicular to the helical axis of DNA in the close vicinity of the phosphate groups. This study, therefore, provides insight into the molecular structure and dynamics of the pre-intercalative outside bound state and will help in understanding the overall intercalation mechanism. |
| Databáze: | OpenAIRE |
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