Ensembles of a small number of conformations with relative populations.

Abstract

In our previous work, we proposed a new way to represent protein native states, using ensembles of a small number of conformations with relative Populations, or ESP in short. Using Ubiquitin as an example, we showed that using a small number of conformations could greatly reduce the potential of overfitting and assigning relative populations to protein ensembles could significantly improve their quality. To demonstrate that ESP indeed is an excellent alternative to represent protein native states, in this work we compare the quality of two ESP ensembles of Ubiquitin with several well-known regular ensembles or average structure representations. Extensive amount of significant experimental data are employed to achieve a thorough assessment. Our results demonstrate that ESP ensembles, though much smaller in size comparing to regular ensembles, perform equally or even better sometimes in all four different types of experimental data used in the assessment, namely, the residual dipolar couplings, residual chemical shift anisotropy, hydrogen exchange rates, and solution scattering profiles. This work further underlines the significance of having relative populations in describing the native states.