The transition matrix is specified with respect to a set of p basis states, χ 1 , χ 2 , ..., χ p which we denote as a vector χ. In what follows, the basis states are assumed to be discrete and orthonormal and each one corresponds to a small region of conformational space. Each frame of an MD trajectory can be mapped to one of these basis states and these discretized MD trajectories form the data from which the transition matrix is estimated.