Speaker
Description
Biological macromolecules, such as DNA duplexes, proteins and polypeptides, comprise many degree of freedom and live in a water environment. Numerical methods have been widely used to study these biological systems, but many of these methods, such as atomistic molecular
dynamics, are rather demanding if many or very large biomolecules are considered. To overcome these limitations, extremely coarse-grained models can be employed, where within these approaches biomolecules retain few degrees of freedom and water is treated implicitly, thus making simulations feasible. A prominent example is provided by G-quadruplexes (G4s), which are helical four-stranded structures forming from guanine-rich nucleic acid sequences and which are thought to play a role in cancer development and malignant transformation. In this seminar I will show examples of extremely coarse-grained modeling of some biomolecules
with special focus on telomeric G4 multimers. Concerning G4s, I will present a novel low-resolution structural approach that combines small-angle X-ray scattering (SAXS) with extremely coarse-grained (ECG) simulations and that allows us to quantify physical properties
of these systems. Complexation of G4 with benchmark ligands, i.e. possible anti-cancer drugs, has been also studied through this approach, proving that it can be an aKordable tool aiding in the selection and design of drugs that target G4s under physiological conditions.