Related Experiment Video
Updated: Oct 24, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Benchmarking Generative AI and Physics-Based Molecular Simulation for Sampling Conformational Heterogeneity in T4
1AlloTec Bio Inc., St. Louis, Missouri63116, United States.
Abstract:
Wild-type T4 lysozyme (T4L) is used as a benchmark to evaluate conformational sampling across generative AI, AI-accelerated molecular simulation (AMS), and physics-based enhanced molecular dynamics (EMD). A four-state model─exposed/open, exposed/closed, buried/open, and buried/closed; is defined using physically meaningful collective variables. Generative AI methods (AF-cluster, MSA subsampling of AlphaFold2, ConforFold, AlphaFlow, ESMFlow, ConfRover, BioEmu) largely sample only the exposed/open state. In contrast, AMS integrates generative ensembles with physics-based molecular simulations, recovering all states and reproducing equilibrium populations similar to EMD and experimental smFRET signatures.
More Related Videos
Related Concept Videos
Gene Families
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Globular and Fibrous Proteins
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...

