Moldrug

Moldrug accelerates hit-to-lead optimization in structure-based drug design by exploring chemical space through structural modifications suggested by the CReM library and optimizing an adaptable fitness function with a genetic algorithm.

Key Features:

• Genetic algorithm optimization: Moldrug employs a genetic algorithm to optimize an adaptable fitness function for molecular design.
• CReM library integration: Moldrug uses structural modifications suggested by the CReM library for ligand binding site exploration and 3D aware molecular enumerations.
• Pre-configured multi-parameter fitness functions: Moldrug offers pre-configured multi-parameter fitness functions for molecular design that balance binding affinity, drug-likeness, and synthetic accessibility.
• External software integration: Moldrug is highly adaptable for integrating functionalities from external software.

Scientific Applications:

• Hit-to-lead optimization: Moldrug accelerates the hit-to-lead phase in structure-based drug design by exploring chemical space around candidate molecules.
• SARS-CoV-2 MPro inhibitor design: Moldrug has been used to design new potential inhibitors targeting the main protease (MPro) of SARS-CoV-2, with designed molecules exhibiting high chemical diversity and predicted binding affinities as low as -10 kcal mol-1 based on MM/GBSA and alchemical binding free energy calculations.

Methodology:

Moldrug explores chemical space using structural modifications suggested by the CReM library and optimizes an adaptable fitness function with a genetic algorithm. Designed molecules can be ranked using MM/GBSA and alchemical binding free energy calculations.