Estimation of Nonlinear Sequence-dependent Constitutive Law for DNA Molecules

Long length-scale structural deformations of DNA play a central role in many biological processes including gene expression. While all-atom based Molecular Dynamics (MD) tools fall short to simulate the long-length and time scale mechanics of DNA, continuum rod model of DNA has emerged as a viable tool. The continuum rod model predictions are however very sensitive to the constitutive law (material properties) of the molecule which, in turn, vary along the molecule's length according to its base-pair sequence. Identification of the sequence-dependent constitutive law from experimental data and feasible all-atom MD simulations remains a significant challenge. The primary goal of the paper is to formulate the general identification problem in a form that is amenable to system identification/estimation methods. To this end, we suggest several simplifications to the continuum rod model of DNA. Finally, we suggest a possible approach to solving the identification problem for a simplified case with a nonlinear constitutive law. A secondary goal of this paper is to bring this important problem to the attention of the system identification community.