We present a novel multi-scale algorithm that make the fully atomistic simulation of bionanosystems over physiologically relevant timescales and conditions, feasible . Our method, termed “NanoX”, is based on the automatic generation of order parameters that describe features of nanoparticle migration, rotation and structural transition. The dynamics equations describe the order parameter evolution over milliseconds or longer with all-atom resolution. NanoX provides insights into the cross-talk between the highly fluctuating atomic motions and the coherent nanoparticle dynamics that underlie many biophysical behaviors.

Viral threats to global health warrant the development of efficient methods to design antiviral drugs and vaccines, and to predict characteristics of mutants of known viruses. Viral structural transitions (STs) constitute a fundamental life-cycle event. They are key to viral infection of a host cell and the maturation of a self-assembling virus.The atomic-scale fluctuations provide the stochastic forces and entropy that drive viral structural transitions, while overall viral structure affects the statistics of atomic fluctuations. The million-atom scale of the viruses and the time and length scales involved in their interaction with host cells, present a grand computational challenge. We present the application of NanoX to the study of cowpea chlorotic mottle virus (CCMV) which is an icosahedral member of the bromovirus group of the Bromoviridae family.

The design of nanocapsules for targeted delivery of therapeutics and imaging systems, presents many, often seemingly self-contradictory, constraints. NanoX predicts the interactions of functionalized nanocapsules with cell surface receptors and with drug, siRNA, gene or other payload. NanoX allows for the simulation of phenomena, such as structural transitions and disassembly of the nanocapsule accompanying timed payload release or due to premature degradation. A novel “salt shaker” effect that underlies fluctuation-enhancement of payload delivery is presented. We also discuss the potential applications of our methodology to the design of nanoparticles for medical imaging.

Central to such a simulation is the interplay between the order parameters and the atomic scale variables which is captured via stochastic equations derived rigorously from the fundamental laws of molecular physics (I.e. Fokker-Planck or Smoluchowski and the corresponding Langevin equations). The thermal average forces and diffusion coefficients that appear in the order parameter dynamics equations, evolve along with the system and are automatically generated within the dynamics loop. NanoX is built on the CHARMM inter-atomic force-field which has been well developed and optimized thus avoiding the need for recalibration of the model for different systems, and is available as free open-source software. Avenues for future development are also discussed.