Millisecond-scale conformational transitions represent a seminal challenge for traditional molecular dynamics simulations, even with the help of high-end supercomputer architectures. Such events are particularly relevant to the study of molecular motors-proteins or abiological constructs that convert chemical energy into mechanical work. Here, we present a hybrid-simulation scheme combining an array of methods including elastic network models, transition path sampling, and advanced free-energy methods, possibly in conjunction with generalized-ensemble schemes to deliver a viable option for capturing the millisecond-scale motor steps of biological motors. The methodology is already implemented in large measure in popular molecular dynamics programs, and it can leverage the massively parallel capabilities of petascale computers. The applicability of the hybrid method is demonstrated with two examples, namely cyclodextrin-based motors and V-type ATPases.