Recent advances in explicit-solvent molecular dynamics simulations of nucleic acids will be overviewed, with a specific emphasis paid to RNA simulations and folding landscape of guanine quadruplex molecules. Recent parametrization efforts of the OL series of nucleic-acids AMBER force fields directed to tuning of non-bonding terms such as addition of the generalized HBfix correction will be introduced. gHBfix is an interaction-specific force-field term that allows convenient weakening and strengthening of selected H-bond interactions and interatomic contacts while minimizing the risk of undesired side-effects. Principal limitations of the nucleic acids force fields will be briefly commented on, together with discussion of inaccuracies of force-field versions currently available in the literature. Further, limitations of collective-variables-based enhanced-sampling simulation methods to describe intrinsically multi-dimensional complex free-energy landscapes of folded nucleic acids will be demonstrated. These limitations are quite often ignored in contemporary literature, leading to publication of unrealistic folding studies missing key parts of free-energy landscapes that remain entirely unvisited in the course of the simulations.

Advances and limitations of MD simulations of nucleic acids: Tuning the non-bonded force-field terms

2019 Spring National Meeting

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