Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Proceedings |
| Conference | Book of Abstracts |
| MU Faculty or unit | |
| Citation | |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | structure; dynamics; nucleic acids |
| Description | Molecular mechanics and dynamics is widely applied to various nucleic acids sequences in order to study their conformational behavior and flexibility. With increasing power of computational methods, it is possible to study structure-functional relationship in more detail. Wide range of methods has been applied to various G-DNA sequences that are able to form four-stranded arrangement. Taking part in controlling function of cells telomeras, these structures are in focus of biomolecular studies for more than 10 years. Computational methods contribute to the experimental ones and help them in prediction and explanation of structural features which can influence quadruplex formation, for example. Starting with conformational search of flexible parts of the molecule interesting conformational possibilities were found. Plain molecular dynamics as well as its modifications such as Locally Enhanced Sampling were used to study stability of geometries found by previous methods or described by experimental studies. Novel methods allow us to analyze the results in order to obtain free energy estimates. Some potential methodological pitfalls can be described by comparing free energy results and conformational preferences suggested for various structural sub-states. In contrast to experimentally observed results free energy analysis found different arrangement as the lowest energy one. Although the methods worked well until now, our results pointed out that still a lot of attention should be payed to methodological (force field) adjustments. Molecular dynamics is a powerful tool, but its routine use without careful attention to force field may be misleading. Anyway, our observations have shown big power of molecular dynamics and relative methods and pointed to potential course of the future methodological development. |
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