Structure prediction techniques free energy modeling

In protein structure prediction, potentials are used to assign an energy-like quantity to a conformation of a protein molecule. If this quantity enables us to distinguish the native state of a protein, the potential is regarded as a reasonable model for a protein-solvent system. The rationale behind this relies on two assumptions (a) a solved protein in its native state can be described by an ensemble of closely related conformations, and (b) in this state the system is in the global minimum of free energy. Virtually all techniques designed for structure prediction are based on these principles [3,4]. 

Here, we review how the development of SAXS as a structural technique is driven by advances in computer algorithms that allow to reconstruct low-resolution electron density maps ab initio from scattering profiles. In addition, we delineate how these low-resolution models can be used in free energy electrostatics calculations. Finally, we discuss how one can exploit the hierarchical nature of RNA folding by combining the low resolution, global information provided by SAXS with local information on RNA structure, from either experiments or state-of-the-art RNA structure prediction algorithms, to further increase the resolution and quality of models obtained from SAXS. 

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