Chapter 4: Treating Biomacromolecular Conformational Variability

The function of a biomacromolecule is related not only to its structure but also to the different conformations that its structural elements can sample. It is therefore important to determine the extent of the structural fluctuations and to identify the states that are actually populated as a result of the rearrangement. However, this accomplishment is undermined by an intrinsic limitation: the amount of experimental data is by and large inferior to the number of the states that a biomacromolecule can actually sample. This means that additional, a priori information must be applied in order to derive the most from the available experimental data but not to run into overinterpretation. In this chapter we will give a summary of the experimental observables that can be used towards the reconstruction of structural ensembles, how the data can be profitably combined and to what extent the data are affected by error; finally we will give an overview of the computational methods that have been developed to model structural ensembles, highlighting their difference and similarities, advantages and disadvantages.