Novel Hits for N-Myristoyltransferase Inhibition Discovered by Docking-Based Screening.

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Drug Discovery

Background:

• N-myristoyltransferase (NMT) inhibitors, initially for parasitic diseases, are promising for cancer therapy.
• Developing selective NMT inhibitors is crucial for clinical advancement.

Purpose of the Study:

• To design a virtual screening protocol to identify novel NMT inhibitors.
• To leverage the common salt bridge interaction in NMT inhibition for drug design.

Main Methods:

• Virtual screening of over 1.1 million compounds from the ZINC database.
• Molecular dynamics simulations to assess inhibitor-NMT complex stability.
• In vitro testing of identified NMT inhibitor candidates.

Main Results:

• Identified several novel NMT inhibitors with potential anti-cancer activity.
• Confirmed the stability of inhibitor-NMT complexes via simulations.
• Some identified ligands demonstrated promising in vitro inhibitory activity.

Conclusions:

• A virtual screening approach based on salt bridge interaction is effective for discovering NMT inhibitors.
• Identified compounds represent promising leads for further optimization in cancer drug development.