The specificity of the interaction between a protein and a small molecule or another protein is also a compromise. We’ve just said that charge–charge and hydrogen-bond interactions don’t contribute a lot to the stability of a protein because their interaction in the folded protein simply replaces their individual interaction with water. The same may be said of the interaction between an enzyme and its substrate or one protein and another. However, there is a huge amount of specificity to be gained in these kinds of interactions. For tight binding, the protein and its ligand must be complementary in every way—size, shape, charge, and hydrogen-bond donor and acceptor sites.
Both the protein and the ligand are solvated by water when they are separated. As the two surfaces interact, water is excluded, hydrogen bonds are broken and formed, hydrophobic interactions occur, and the protein and ligand stick to each other. As in protein folding and for the same reasons, the hydrophobic interaction provides much of the free energy for the association reaction, but polar groups that are removed
Both the protein and the ligand are solvated by water when they are separated. As the two surfaces interact, water is excluded, hydrogen bonds are broken and formed, hydrophobic interactions occur, and the protein and ligand stick to each other. As in protein folding and for the same reasons, the hydrophobic interaction provides much of the free energy for the association reaction, but polar groups that are removed
ASSOCIATION:-
The association of two molecules uses the same interactions that stabilize a protein’s structure: hydrophobic interactions, van der Waals interactions, hydrogen bonds, and ionic interactions. To get the most out of the interaction, the two molecules must be complementary.
Consider what happens when a nonoptimal ligand binds to the protein. The binding of this modified ligand is much weaker not because it’s not the right size to fit into the protein-binding site, but because the complementary group on the protein loses a favorable interaction with water that is not replaced by an equally favorable interaction with the ligand
The association of two molecules uses the same interactions that stabilize a protein’s structure: hydrophobic interactions, van der Waals interactions, hydrogen bonds, and ionic interactions. To get the most out of the interaction, the two molecules must be complementary.
Consider what happens when a nonoptimal ligand binds to the protein. The binding of this modified ligand is much weaker not because it’s not the right size to fit into the protein-binding site, but because the complementary group on the protein loses a favorable interaction with water that is not replaced by an equally favorable interaction with the ligand
As with the formation of secondary structure, the multiple, cooperative hydrogen bonds that can be formed between the ligand and the protein may be stronger and more favorable than hydrogen bonds that the ligand might make to water. Hydrogen bonding may, in fact, make some contribution to the favorable free energy of binding of ligands to proteins.
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