FastConformation

FastConformation integrates MSA generation, AlphaFold2 structure prediction, and conformational ensemble analysis to predict and analyze protein conformational ensembles through MSA subsampling.

Key Features:

• MSA Generation: Generates multiple sequence alignments from amino acid sequences as input for structure prediction.
• AlphaFold2 Structure Prediction: Predicts protein structures using AlphaFold 2 (AF2) with subsampled MSAs to generate alternative conformations.
• Conformational Ensemble Analysis: Analyzes protein conformations and their distributions interactively.
• Iterative Subsampling Refinement: Allows users to refine subsampling parameters based on analyses to achieve diverse conformational ensembles.
• High-Throughput Processing: Generates predictions and analyses in hours on local machines.

Scientific Applications:

• Kinase Conformational Modeling: Predicts conformational ensembles of proteins such as Abl1 kinase.
• Transporter Conformational Modeling: Predicts conformational ensembles of proteins such as LAT1 transporter.
• GPCR Conformational Modeling: Predicts conformational ensembles of proteins such as CCR5 receptor.
• Mutation Effect Analysis: Analyzes effects of mutations on protein conformational ensembles.
• Protein Biochemistry: Enables high-throughput applications in protein biochemistry research.
• Drug Discovery: Supports drug discovery applications through conformational ensemble generation.
• Protein Engineering: Supports protein engineering applications through conformational ensemble generation.

Methodology:

FastConformation uses MSA subsampling to manipulate multiple sequence alignment inputs into AlphaFold 2, generating conformational ensembles of proteins from amino acid sequences.