Hydrogen Bond (H-bond)

A non-covalent interaction between a hydrogen atom bonded to an electronegative atom (donor) and a lone pair on another electronegative atom (acceptor). In drug-receptor interactions, hydrogen bonds provide directional specificity and contribute 1-7 kcal/mol per bond to binding affinity. The number of hydrogen bond donors and acceptors is a critical parameter in Lipinski's Rule of Five for predicting oral bioavailability.

Örnekler

• Lipinski limits: no more than 5 H-bond donors and 10 H-bond acceptors for oral drugs
• ACE inhibitors: critical H-bonds with zinc-coordinating residues in the active site
• Methotrexate: multiple H-bonds mimic dihydrofolate binding to DHFR enzyme