Frog: a FRee Online druG 3D conformation generator

Area of Science:

• Computational Chemistry
• Drug Discovery
• Cheminformatics

Background:

• In silico screening methods are crucial for drug discovery, requiring 3D structures of ligands and proteins.
• Generating multi-conformer 3D models is essential for efficient virtual screening and docking studies.
• Many compound collections are available in 1D SMILES or 2D SDF formats, necessitating 1D/2D to 3D conversion tools.

Purpose of the Study:

• To introduce Frog, an online service for generating 3D conformations of drug-like compounds from 1D or 2D descriptions.
• To provide a free and accessible tool for creating 3D molecular models required for computational drug discovery.

Main Methods:

• Frog utilizes atomic constitution and connectivity information to identify molecular isomers.
• It employs an assembly process to generate single or multiple low-to-medium energy 3D conformations.
• The method does not currently account for ring flexibility in its conformational generation.

Main Results:

• Frog successfully generates 3D conformations for drug-like compounds from 1D/2D input formats.
• Generated conformations are shown to be close to experimentally observed bioactive structures in crystallographic complexes.
• The service provides an efficient way to obtain necessary 3D models for virtual screening.

Conclusions:

• Frog is a valuable free online resource for generating 3D molecular conformations.
• It addresses the need for 1D/2D to 3D structure generation in drug discovery workflows.
• The tool facilitates virtual screening and other structure-based computational studies.