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?S. Entropy, roughly, describes the disorder of a system. Highly ordered states, such as protein crystals, are disfavored thermodynamically compared to more disordered states, such as solutions of proteins in solvent, because the transition to a more ordered state would decrease the total entropy of the system (negative ?S). For crystals to form spontaneously, the ?G of crystal formation must be negative. In other words, the entropic penalty must be paid by a corresponding decrease in the total energy of the system (?H). Familiar inorganic crystals

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