Abstract
Protein functional mechanisms usually require conformational changes, and often there are known structures for the different conformational states. However, usually neither the origin of the driving force nor the underlying pathways for these conformational transitions is known. Exothermic chemical reactions may be an important source of forces that drive conformational changes. Here we investigate this type of force originating from ATP hydrolysis in the chaperonin GroEL, by applying forces originating from the chemical reaction. Specifically, we apply directed forces to drive the GroEL conformational changes and learn that there is a highly specific direction for applied forces to drive the closed form to the open form. For this purpose, we utilize coarse-grained elastic network models. Principal component analysis on 38 GroEL experimental structures yields the most important motions, and these are used in structural interpolation for the construction of a coarse-grained free energy landscape. In addition, we investigate a more random application of forces with a Monte Carlo method and demonstrate pathways for the closed-open conformational transition in both directions by computing trajectories that are shown upon the free energy landscape. Initial root mean square deviation (RMSD) between the open and closed forms of the subunit is 14.7 Å and final forms from our simulations reach an average RMSD of 3.6 Å from the target forms, closely matching the level of resolution of the coarse-grained model.