Dimensionality of Collective Variables for Describing Conformational Changes of a Multi-Domain Protein.

Collective variables (CVs) are often used in molecular dynamics simulations based on enhanced sampling algorithms to investigate large conformational changes of a protein. The choice of CVs in these simulations is essential because it affects simulation results and impacts the free-energy profile, the minimum free-energy pathway (MFEP), and the transition-state structure. Here we examine how many CVs are required to capture the correct transition-state structure during the open-to-close motion of adenylate kinase using a coarse-grained model in the mean forces string method to search the MFEP. Various numbers of large amplitude principal components are tested as CVs in the simulations. The incorporation of local coordinates into CVs, which is possible in higher dimensional CV spaces, is important for capturing a reliable MFEP. The Bayesian measure proposed by Best and Hummer is sensitive to the choice of CVs, showing sharp peaks when the transition-state structure is captured. We thus evaluate the required number of CVs needed in enhanced sampling simulations for describing protein conformational changes.