Download PDFOpen PDF in browserAnalysis of AlphaFold2 for Modeling Structures of Wildtype and Variant Protein Sequences13 pages•Published: March 22, 2022AbstractResNet and, more recently, AlphaFold2 have demonstrated that deep neural networks can now predict a tertiary structure of a given protein amino-acid sequence with high accuracy. This seminal development will allow molecular biology researchers to advance various studies linking sequence, structure, and function. Many studies will undoubtedly focus on the impact of sequence mutations on stability, fold, and function. In this paper, we evaluate the ability of AlphaFold2 to predict accurate tertiary structures of wildtype and mutated sequences of protein molecules. We do so on a benchmark dataset in mutation modeling studies. Our empirical evaluation utilizes global and local structure analyses and yields several interesting observations. It shows, for instance, that AlphaFold2 performs similarly on wildtype and variant sequences. The placement of the main chain of a protein molecule is highly accurate. However, while AlphaFold2 reports similar confidence in its predictions over wildtype and variant sequences, its performance on placements of the side chains suffers in comparison to main-chain predictions. The analysis overall supports the premise that AlphaFold2-predicted structures can be utilized in further downstream tasks, but that further refinement of these structures may be necessary.Keyphrases: alphafold2, protein tertiary structure, structure quality analysis In: Hisham Al-Mubaid, Tamer Aldwairi and Oliver Eulenstein (editors). Proceedings of 14th International Conference on Bioinformatics and Computational Biology, vol 83, pages 53-65.
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