Table 3.

Classification of additives according to McPherson et al. [35].

Molecule	Category
Natural additives	Physiologically or biochemically relevant small molecules, such as coenzymes, substrate analogues, inhibitors, metal cofactors, or prosthetic groups
Chemical protectants	Molecules that assure protein integrity such as reductants and metal atoms scavengers
Solubilizing agents and detergents	Mild non-detergent molecules, such as sulfobetaines, low concentrations of chaotropic agents and surfactants and, in the case of membrane proteins, stronger solubilizing agents such as detergents
Poisons	Agents that partially inhibit nucleation thus facilitating the growth of few crystals of high quality, such as DMSO, DMF, low weigh alcohols and sugars
Osmolytes	Natural occurring molecules that help the protein in the adaptation to osmotic stress while maintaining native structure and function, such as TMAO, sarcosine and betaine
Non-covalent cross-linkers	Molecules able to stabilize the crystal lattice by mediating sample aggregation through reversible intermolecular interactions, electrostatic or hydrophobic, among surface groups on neighboring protein molecules
Covalent cross-linkers	Crosslinking reagents that may both reduce the conformational protein mobility and the stability of a protein-ligand complex