Ample

Ample generates search ensembles from ab initio protein models to facilitate molecular replacement in X-ray crystallography.

Key Features:

• Ab Initio Model Generation: Generates initial protein models directly from amino acid sequences.
• Rosetta-based Modeling: Utilizes locally installed Rosetta to perform initial model building.
• Clustering and Truncation Pipeline: Clusters multiple ab initio models and quantitatively assesses local accuracy to form candidate ensembles.
• Rational Model Refinement: Identifies and truncates regions with predicted inaccuracies to refine ensembles for molecular replacement.
• Side-chain Addition: Refined ensembles can include rapidly added side chains to enhance suitability for molecular replacement.
• Input Data Types: Accepts FASTA sequence files and diffraction data as input.
• Integration with CCP4 Suite: Integrates with the CCP4 suite of crystallographic tools.

Scientific Applications:

• Molecular Replacement: Produces search ensembles used to solve crystal structures by molecular replacement when experimental phase information is unavailable.
• Structural Genomics and Difficult Phasing Cases: Supports determination of protein structures that are challenging due to limited experimental phase information.
• Performance Benchmarking: Demonstrated success rates of 43% overall and 80% for all-α proteins on test sets.

Methodology:

Inputs are a FASTA sequence file and diffraction data; AMPLE uses locally installed Rosetta to generate ab initio models, clusters those models to form ensembles, truncates inaccurately predicted regions to optimize ensembles, and can add side chains to the refined ensembles.