A line integral reaction path approximation for large systems via nonlinear constrained optimization: application to...

A variation of the line integral method of Elber with self-avoiding walk has been implemented using a state of the art nonlinear constrained optimization procedure. The new implementation appears to be robust in finding approximate reaction paths for small and large systems. Exact transition states and intermediates for the resulting paths can easily be pinpointed with subsequent application of the conjugate peak refinement method [S. Fischer and M. Karplus, Chem. Phys. Lett. 194, 252 (1992)] and unconstrained minimization, respectively. Unlike previous implementations utilizing a penalty function approach, the present implementation generates an exact solution of the underlying problem. Most importantly, this formulation does not require an initial guess for the path, which makes it particularly useful for studying complex molecular rearrangements. The method has been applied to conformational rearrangements of the alanine dipeptide in the gas phase and in water, and folding of the beta hairpin of protein G in water. In the latter case a procedure was developed to systematically sample the potential energy surface underlying folding and reconstruct folding pathways within the nearest-neighbor hopping approximation.