Predicting the dynamic behaviour of a muscle fibre containing a heterogeneous mixture of isoforms (e.g. fast and slow isoforms mutant and wt protein) is difficult since responses may be non-linear. We have implemented in a computational platform MUSICO the ability to predict the transient responses for a muscle fibre containing a variable ratio of isoforms based on the properties of pure isoforms. The MUSICO platform traces the action of each myosin head or regulatory protein in the 3D sarcomere lattice and quantitatively predicts muscle fiber responses for various calcium transients and mechanical loading conditions. The modular set up of the software provides an opportunity to distribute different isoforms randomly or in an ordered fashion and associate each isoform with its appropriate kinetic properties. For the prediction of mechanical and energetic response of variable ratios of human alpha and beta myosin isoforms we established an eight step ATPase cycle and allow actin, myosin, substrate ATP and product ADP & Pi concentrations to be fixed or varied. From the experiments in solution we extracted realistic rate constants to each step of the cycle for any well-defined myosin isoform. The MUSICO prediction for various ratios of alpha and beta myosin isoforms shows that in a steady state the mechanical and energetic (e.g. ATPase) responses are proportional to the ratio of the isoform concentrations. However, the response to rapid changes in calcium concentrations (twitch or during force development and relaxation) we observed that: (i) during the fast rise in force the response is biased toward the fast isoform and (ii) during relaxation toward the slow isoform response. Overall, this approach will be a useful tool to explore the behavior of different mixed myosin and troponin populations.