Sequence clustering confounds AlphaFold2

Main Topic: A critical evaluation of AF-cluster, a method used to predict the structures of metamorphic proteins with AlphaFold2 (AF2). Key Points: Metamorphic proteins can adopt multiple stable conformations, making their structure prediction challenging. AF-cluster, initially presented as a solution, is called into question by Schafer et al. due to: Inaccurate predictions compared to random sampling. Misidentification of non-metamorphic proteins and erroneous conformation predictions. Discrepancies in confidence scores for predicted structures. CF-random, a method using ColabFold with random MSAs, is introduced as a more reliable and efficient alternative. The study highlights the need for: Rigorous validation of computational predictions. Complementary approaches for accurate protein structure prediction. Transparency in methodology to facilitate further research.