af3cli: Streamlining AlphaFold3 Input Preparation

Abstract

With the release of AlphaFold3, modeling capabilities have expanded beyond protein structure prediction to embrace the inherent complexity of biomolecular systems, including nucleic acids, ions, small molecules, and their interactions. The increased complexity of these assemblies is reflected in the input file generation process, presenting a significant hurdle for researchers without advanced computational expertise. While AlphaFold Server comes with a user-friendly graphical user interface, it supports only a subset of the features of AlphaFold3. To address this, we present af3cli, an open-source tool designed to facilitate the generation of AlphaFold3 input files, specifically tailored to the standalone version of AlphaFold3 and its unrestricted functionality. Featuring a user-friendly command-line interface and an accompanying Python library, af3cli simplifies the input generation process while maintaining flexibility and customization, which makes af3cli especially useful for fast (automated) generation of a large number of input files since it enables direct incorporation of FASTA files, keeps track of IDs, and validates the JSON file. Through practical examples, we demonstrate its capabilities for constructing input data for diverse biological structures, ranging from simple proteins to complex systems, and demonstrate its seamless integration into both manual and automated workflows.