Hydrogen bonding and biological specificity analysed by protein engineering

Abstract
The role of complementary hydrogen bonding as a determinant of biological specificity has been examined by protein engineering of the tyrosyl-tRNA synthetase. Deletion of a side chain between enzyme and substrate to leave an unpaired, uncharged hydrogen-bond donor or acceptor weakens binding energy by only 0.5–1.5 kcal mol−1. But the presence of an unpaired and charged donor or acceptor weakens binding by a further ∼ 3 kcal mol−1.