Multiple Target Drug Design Using LigBuilder 3.

Area of Science:

• Computational chemistry
• Medicinal chemistry
• Drug discovery

Background:

• Treating complex diseases requires drugs targeting multiple molecular pathways.
• Multi-target-directed ligands (MTDLs) offer a promising therapeutic strategy.
• Developing diverse and complex MTDLs is crucial for efficacy.

Purpose of the Study:

• To present a computational protocol for designing MTDLs.
• To introduce LigBuilder 3, a novel de novo multi-target drug design program.
• To demonstrate the protocol's utility in designing dual-functional compounds.

Main Methods:

• Utilizing LigBuilder 3, which integrates binding site prediction, de novo design, and optimization modules.
• Employing fragments from known inhibitors to construct novel molecules.
• Applying the protocol to design compounds targeting HIV protease (PR) and reverse transcriptase (RT).

Main Results:

• Successful design of dual-functional compounds targeting two distinct viral enzymes.
• Demonstration of LigBuilder 3's capability in generating complex MTDLs.
• Validation of the computational approach for MTDL development.

Conclusions:

• The described computational protocol and LigBuilder 3 provide an effective strategy for MTDL development.
• This approach facilitates the creation of diverse chemical entities for complex disease treatment.
• The de novo design method enhances the complexity and diversity of potential drug candidates.