Necessity of triangle updates and pair-representation interactions for high-performance protein folding

Determine whether the architectural components introduced in AlphaFold2—specifically triangle update modules and explicit modeling of interactions between single and pair representations—are necessary conditions to achieve high performance in protein structure prediction, as opposed to general-purpose transformer architectures that omit these components.

Background

AlphaFold2 and related folding models incorporate domain-specific architectural elements such as triangle updates and explicit pair representations to model interactions between residues, which have been widely adopted as a standard design in protein folding systems.

SimpleFold departs from these designs by using only general-purpose transformer blocks without explicit pair representations or triangle modules, yet it reports competitive performance. Despite this empirical evidence, the necessity of such domain-specific components for achieving high accuracy remains explicitly open, motivating a systematic investigation of their role and potential alternatives.