Grein, S.; Penas, D. R.; Weindl, D.; Lakrisenko, P.; Banga, J. R.; Hasenauer, J.

Dynamic models are central to the computational life sciences but typically contain unknown parameters that must be inferred from experimental data. High-throughput measurements have made this task increasingly challenging, yielding high-dimensional search spaces and non-convex objectives with many local optima. This makes the choice of optimisation method critical. However, existing empirical studies either consider only a limited number of benchmark problems or only a narrow spectrum of local, global and hybrid optimisation methods. Here, we present a comprehensive benchmark of a broad range of optimisation methods on a curated collection of parameter estimation problems, comprising 990 method-problem-pairs executed on two independent supercomputing infrastructures. Our evaluation quantifies success rates, solution quality and computational cost, revealing characteristic strengths and limitations of each approach. We find that optimisation methods separated into clear performance tiers. Building on these results, we implemented a new hybrid strategy that combines enhanced scatter search with the best-performing local solver, which showed robust performance and improved on the other scatter-search variants we tested. Our results provide practical guidance for selecting optimisation methods and thereby support more accurate and reliable model calibration.