Title : Coarse-grained models of nucleic acids and their applications
All-atom molecular dynamics (MD) simulations have been proved as a valuable tool providing insight into biomolecular processes at the atomic resolution. Despite the enormous growth of computing power since all-atom MD simulations of proteins were introduced at the end of 70’s there are still many biological phenomena with time-scales which are beyond the reach of all-atom MD models. This was the main motivation for development of so-called coarse-grained models of proteins and nucleic-acids in which groups of atoms are replaced by special interaction centers. Properly designed coarse-grained models of nucleic acids were able to give insight into many important long-scale biological processes like: double-helix formation, G-quadruplex formation or RNA tertiary structure formation.
The basics of methodology of construction of coarse-grained models of nucleic acids will be presented. The strength and weaknesses of two qualitatively different design strategies – physics and statistics-based – will be discussed. In particular three differently designed coarse-grained models of nucleic acids will be presented: physics-based dipolar-bead model; physics/statistics based NARES-2P model and statistics-based SimDNA. Several applications of different coarse-grained models of nucleic acids will be presented. The dipolar-bead model was used to obtain atomic-level insight into the process of formation of DNA double-helix. NARES-2P model was applied to explain specific physical properties of telomeric structures. Finally SimDNA model, which is still under development, was applied to the process of formation of DNA G-quadruplexes.
Audience take away:
• How to apply coarse-graining methodology to biological polymers.
• How to use coarse-grained models to predict structure of nucleic acids.
• How to use coarse-grained models to study the processes of folding/unfolding of nucleic acids.