Simulations can provide tremendous insight into atomistic details of biological mechanisms, but micro- to milliseconds timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative, bringing long-timescale processes within reach of a broader community. We used Google’s Exacycle cloud computing platform to simulate an unprecedented 2 milliseconds of dynamics of the β2 adrenergic receptor (β2AR)—a major drug target G protein-coupled receptor (GPCR). Markov state models aggregating independent simulations into a single statistical model are validated by previous computational and experimental results. Moreover, our models provide the first atomistic description of the activation of a GPCR, revealing multiple activation pathways. Agonists and inverse agonists interact differentially with these pathways, with profound implications for drug design.