Combined Newton-Gradient Method for Constrained Root-Finding in Chemical Reaction Networks

Abstract

In this work, we present a fast, globally convergent, iterative algorithm for computing the asymptotically stable states of nonlinear large-scale systems of quadratic autonomous ordinary differential equations (ODE) modeling, e.g., the dynamic of complex chemical reaction networks. Toward this aim, we reformulate the problem as a box-constrained optimization problem where the roots of a set of nonlinear equations need to be determined. Then, we propose to use a projected Newton’s approach combined with a gradient descent algorithm so that every limit point of the sequence generated by the overall algorithm is a stationary point. More importantly, we suggest replacing the standard orthogonal projector with a novel operator that ensures the final solution to satisfy the box constraints while lowering the probability that the intermediate points reached at each iteration belong to the boundary of the box where the Jacobian of the objective function may be singular. The effectiveness of the proposed approach is shown in a practical scenario concerning a chemical reaction network modeling the signaling network of colorectal cancer cells. Specifically, in this scenario the proposed algorithm is proved to be faster and more accurate than a classical dynamical approach where the asymptotically stable states are computed as the limit points of the flux of the Cauchy problem associated with the ODE system.