Low frequency vibrational modes that are thermally excited at room temperature can provide critical insights into conformational changes of proteins. However, current state-of-the-art methods for their analysis in computational models are limited by harmonic approximations that fail to capture the pronounced anharmonic nature of such vibrational modes. In this talk, I will discuss current procedures for the analysis of collective degrees of freedom associated with internal vibrations. Then, I will introduce a new time correlation formalism that eliminates the need for harmonic or quasi-harmonic approximations and thus fully captures the anharmonic properties of low frequency vibrations and diffusional processes in complex molecular systems.