In Silico Single-Molecule Manipulation of DNA with Rigid Body Dynamics

We develop a new powerful method to reproduce in silico single-molecule manipulation experiments. We demonstrate that flexible polymers such as DNA can be simulated using rigid body dynamics thanks to an original implementation of Langevin dynamics in an open source library called Open Dynamics Engine. We moreover implement a global thermostat which accelerates the simulation sampling by two orders of magnitude. We reproduce force-extension as well as rotation-extension curves of reference experimental studies. Finally, we extend the model to simulations where the control parameter is no longer the torsional strain but instead the torque, and predict the expected behavior for this case which is particularly challenging theoretically and experimentally.Author Summary: Video game techniques are designed to simulate rigid body dynamics of macroscopic bodies, e.g. characters or vehicles, in a realistic manner. However they are not able to deal with temperature effects, hence they are not able to deal with molecules. In order to extend these powerful techniques to molecular modeling, we implement here Langevin Dynamics in an open source library called Open Dynamics Engine. Moreover we add a “global thermostat” to this Langevin Dynamics, which accelerates the simulation sampling by two orders of magnitude. With these radically new simulation techniques, we prove that we can accurately reproduce single-molecule manipulation experiments in silico, in particular force-extension as well as rotation-extension curves of reference experimental studies. The method developed here represents an unparalleled tool for the study of more complex single molecule manipulation experiments, notably when DNA interacts with proteins. Furthermore the simulation technique that we propose here has all the functionalities required to tackle the nuclear organization of chromosomes at every length scale, from DNA to whole nuclei.