The goal of this project is to complete the development of the MBO(N)D (Multi-Body Order (N) Dynamics) molecular dynamics (MD) simulation method specifically for nucleic acid applications (e.g., DNA, RNA), such as encountered in anticancer drug research. MBO(N)D's unique approach of substructuring molecules into flexible and/or rigid bodies allows MBO(N)D to take long time steps, yielding factors of 100 or more in computational speed compared to all-atom methods. This offers a new and efficient route to stable long time duration trajectories from which reliable structural stabilities, free energies and binding potentials can be calculated. The primary Phase II objective is to develop and evaluate generalizable MBO(N)D substructuring schemes for oligonucleotides, solvent and salt. This is key to ultimate widespread scientific utility and commercialization of MBO(N)D. A series of single, duplex and triplex test cases (including solvent and counterions) will be analyzed in an effort to develop suitable substructuring schemes that maximize MBO(N)D's computational speed, while maintaining accurate essential dynamics. Accuracy evaluations will consist of comparison with all-atom ensemble statistics, including RMS position and angle fluctuations, free energy, and others.
Successful completion of this project will result in a highly efficient software code, MBO(N)D/NAD (Nucleic Acid Dynamics), specifically tailored for oligonucleotides. It will allow the long time duration simulations required for reliable structural stabilities, free energies, and binding potentials. Such a capability is in high demand by anticancer and other nucleic acid drug researchers.