Rigid Base Biasing in Molecular Dynamics enables enhanced sampling of DNA conformations

TL;DR

The paper introduces RBB-NA, an algorithm that applies biasing potentials to control rigid base parameters in all-atom nucleic acid simulations, enabling enhanced sampling of diverse DNA conformations and mechanics.

Contribution

It presents a novel algorithm for controlling rigid base parameters in all-atom simulations, facilitating exploration of highly deformed nucleic acid structures.

Findings

RBB-NA accurately reproduces unconstrained simulation data.

It enables exploration of anharmonic DNA mechanics.

The method captures complex deformations like twisting and buckling.

Abstract

All-atom simulations have become increasingly popular to study conformational and dynamical properties of nucleic acids as they are accurate and provide high spatial and time resolutions. This high resolution however comes at a heavy computational cost and within the time scales of simulations nucleic acids weakly fluctuate around their ideal structure exploring a limited set of conformations. We introduce the RBB-NA algorithm which is capable of controlling rigid base parameters in all-atom simulations of Nucleic Acids. With suitable biasing potentials this algorithm can "force" a DNA or RNA molecule to assume specific values of the six rotational (tilt, roll, twist, buckle, propeller, opening) and/or the six translational parameters (shift, slide, rise, shear, stretch, stagger). The algorithm enables the use of advanced sampling techniques to probe the structure and dynamics of locally strongly deformed Nucleic Acids. We illustrate its performance showing some examples in which DNA is strongly twisted, bent or locally buckled. In these examples RBB-NA reproduces well the unconstrained simulations data and other known features of DNA mechanics, but it also allows one to explore the anharmonic behavior characterizing the mechanics of nucleic acids in the high deformation regime.