Background: Hormone based birth control often causes various side effects. A recent study
revealed that temporary infertility without changing hormone levels can be attained by inhibiting
Katanin p60 ATPase-containing subunit A-like 1 protein (KATNAL1) which is critical for sperm
maturation in the testes.
Objective: This study aimed at attaining the most energetically stable three dimensional (3D) structure
of KATNAL1 protein using comparative modeling followed by screening of a ligand library of known
natural spermicidal compounds for their binding affinity with KATNAL1. This in turn may inhibit the
development of mature sperm in the seminiferous epithelium.
Method: A series of computational techniques were used for building the 3D structure of KATNAL1
which was further optimized by molecular dynamics (MD) simulation. For revealing the ATP binding
mode of KATNAL1, docking study was carried out using the optimized model obtained from the MD
simulation. The docking study was also employed to test the binding efficiency of the ligand library.
Results: Molecular docking study confirmed the ATP binding of KATNAL1 with various hydrophobic
and hydrogen bond interactions. Binding efficiency of the ligand library suggested that calotropin, a
cardenolide of Calotropis procera showed the highest binding efficiency against the target protein
without toxicity. MD simulation of the docked complex validated the results of the docking study.
Conclusion: This study revealed the ATP binding mode of KATNAL1 and identified calotropin as a
potential lead molecule against it showing high binding efficiency with good bioavailability and no
mutagenicity. Further in vitro and in vivo bioassay of calotropin could facilitate the development of
novel non-hormonal male-specific contraceptive in near future.