Computational insight into novel molecular recognition mechanism of different bioactive GAs and the Arabidopsis...

Gibberellin (GA) is an essential plant hormone and plays a significant role during the growth and development of the higher plants. The molecular recognition mode between GA and receptor Arabidopsis thaliana GIBBERELLIN INSENSITIVE DWARF1 A (AtGID1A) was investigated by molecular docking and dynamics simulations to clarify the selective perceived mechanism of different bioactive GA molecules to AtGID1A. The 6-COOH group of GA, especially its β configuration, was found to be an indispensable pharmacophore group for GA recognition and binding to AtGID1A. Not only does a strong salt bridge interaction between the 6β-COOH group of GA and Arg244 of AtGID1A play a very important role in the GA recognition of the receptor, but also an indirect water bridge interaction between the pharmacophore group 6β-COOH of GA and the residue Tyr322 of AtGID1A is essential for the GA binding to the receptor. The site-directed residues mutant modeling study on the receptor-binding pocket confirmed that the mutations of Arg244 and Tyr322 decreased the GA binding activity due to the disappearances of the salt bridge and the hydrogen bond interaction. The 3β-OH group of GA was well known to be necessary for the GA bioactivity due to its forming a unique hydrogen bond with Tyr127 of AtGID1A. In addition, the hydrophobic interaction between GA and AtGID1A was considered a necessary factor to lock the GA active conformation and stabilize the GA-GID1A complex structure. The novel molecular recognition mode will be beneficial in elucidating the GA regulation function on the growth and development of the higher plants.