Automated identification of chalcogen bonds in AlphaFold protein structure database files: is it possible?

ABSTRACT

Protein structure prediction and structural biology have entered a new era with an artificial intelligence-based approach encoded in the AlphaFold2 and the analogous RoseTTAfold methods. More than 200 million structures have been predicted by AlphaFold2 from their primary sequences and the models as well as the approach itself have naturally been examined from different points of view by experimentalists and bioinformaticians. Here, we assessed the degree to which these computational models can provide information on subtle structural details with potential implications for diverse applications in protein engineering and chemical biology and focused the attention on chalcogen bonds formed by disulphide bridges. We found that only 43% of the chalcogen bonds observed in the experimental structures are present in the computational models, suggesting that the accuracy of the computational models is, in the majority of the cases, insufficient to allow the detection of chalcogen bonds, according to the usual stereochemical criteria. High-resolution experimentally derived structures are therefore still necessary when the structure must be investigated in depth based on fine structural aspects.