Satisfaction of hydrogen-bonding potential influences the conservation of polar sidechains.

Although polar amino acids tend to be found on the surface of proteins due to their hydrophilic nature, their important roles within the core of proteins are now becoming better recognized. It has long been understood that a significant number of mainchain functions will not achieve hydrogen bond satisfaction through the formation of secondary structures; in these circumstances, it is generally buried polar residues that provide hydrogen bond satisfaction. Here, we describe an analysis of the hydrogen-bonding of polar amino acids in a set of structurally aligned protein families. This allows us not only to calculate the conservation of each polar residue but also to assess whether conservation is correlated with the hydrogen-bonding potential of polar sidechains. We show that those polar sidechains whose hydrogen-bonding potential is satisfied tend to be more conserved than their unsatisfied or nonhydrogen-bonded counterparts, particularly when buried. Interestingly, these buried and satisfied polar residues are significantly more conserved than buried hydrophobic residues. Forming hydrogen bonds to mainchain amide atoms also influences conservation, with those satisfied buried polar residues that form two hydrogen bonds to mainchain amides being significantly more conserved than those that form only one or none. These results indicate that buried polar residues whose hydrogen-bonding potential is satisfied are likely to have important roles in maintaining protein structure.