Markov state modeling of binding and conformational changes of proteins Proteins are molecules that are essential for life and carry out an enormous number of functions in organisms. To this end they change their conformation and bind to other molecules. However the interplay between conformational change and binding is not fully understood. In this work this interplay is investigated with molecular dynamics (MD) simulations of the protein peptide system Mdm2 PMI and by analysis of data from relaxation experiments. The central task it to uncover the binding mechanism which is described by the sequence of (partial) binding events and conformational change events including their probabilities. In the simplest case the binding mechanism is described by a two step model: binding followed by conformational change or conformational change followed by binding. In the general case longer sequences with multiple conformational changes and partial binding events are possible as well as parallel pathways that differ in their sequences of events. The theory of Markov state models (MSMs) provides the ...