Artificial intelligence for template-free protein structure prediction: a comprehensive review - Artificial Intelligence Review

Protein structure prediction (PSP) is a grand challenge in bioinformatics, drug discovery, and related fields. PSP is computationally challenging because of an astronomically large conformational space to be searched and an unknown very complex energy function to be minimised. To obtain a given protein's structure, template-based PSP approaches adopt a similar protein's known structure, while template-free PSP approaches work when no similar protein's structure is known. Currently, proteins with known structures are greatly outnumbered by proteins with unknown structures. Template-free PSP has obtained significant progress recently via machine learning and search-based optimisation approaches.