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.