Automated site-directed drug design using molecular lattices

Area of Science:

• Computational chemistry
• Drug discovery
• Molecular modeling

Background:

• Receptor-based drug design relies on understanding receptor structure and molecular recognition principles.
• Drug-receptor interactions are often governed by specific key receptor groups.
• A common challenge is assembling molecular fragments into structures that fit receptor binding sites.

Purpose of the Study:

• To present a novel computational program, BUILDER, for generating diverse molecular structures.
• To demonstrate a new approach for fragment-based drug design within an interactive modeling environment.
• To showcase the program's utility in designing molecules for specific targets like HIV-1 protease.

Main Methods:

• Utilizing database searching techniques and structure generation algorithms.
• Integrating these methods within an interactive graphics modeling environment (MidasPlus).
• Introducing a novel tool for process communication called delegate.

Main Results:

• The BUILDER program successfully combines database searching and structure generation.
• The delegate tool facilitates efficient process communication within the modeling environment.
• Demonstrated the generation of novel molecular structures complementary to the HIV-1 protease active site.

Conclusions:

• BUILDER offers a powerful new tool for receptor-based drug design.
• The program facilitates the creation of diverse and complementary molecular structures.
• This approach aids in the rational design of novel drug candidates for specific biological targets.