Many biophysical systems and proteins undergo mesoscopic conformational changes in order to perform their biological function. However, these conformational changes often result from a cascade of atomistic interactions within a much larger overall object. For simulations of such systems, the computational cost of retaining high-resolution structural and dynamical information whilst at the same time observing large scale motions over long times is high. Furthermore, this cost is only going to increase as ever larger biological objects are observed experimentally at high resolution.With insight from the theory of Markov state models and transition state theory, we derive a generalised mechano-kinetic simulation framework which aims to compensate for these disparate time scales. The framework models continuous dynamical motion at coarse-grained length scales whilst simultaneously including fine-detail, chemical reactions or conformational changes implicitly using a kinetic model. The kinetic model is coupled to the dynamic model in a highly generalised manner, such that it can be applied to any defined continuous energy landscape, and indeed, any existing dynamic simulation framework. We present a series of analytical examples to validate the framework, and showcase its capabilities for studying more complex systems by designing a simulation of minimalist molecular motor.