  Performing full-resolution atomistic simulations of nucleic acid folding has
remained a challenge for biomolecular modeling. Understanding how nucleic acids
fold and how they transition between different folded structures as they unfold
and refold has important implications for biology. This paper reports a
theoretical model and computer simulation of the ab initio folding of DNA
inverted repeat sequences. The formulation is based on an all-atom
conformational model of the sugar-phosphate backbone via chain closure, and it
incorporates three major molecular-level driving forces - base stacking,
counterion-induced backbone self-interactions and base pairing - via separate
analytical theories designed to capture and reproduce the effects of the
solvent without requiring explicit water and ions in the simulation. To
accelerate computational throughput, a mixed numerical/analytical algorithm for
the calculation of the backbone conformational volume is incorporated into the
Monte Carlo simulation, and special stochastic sampling techniques were
employed to achieve the computational efficiency needed to fold nucleic acids
from scratch. This paper describes implementation details, benchmark results
and the advantages and technical challenges with this approach.
