FoldDelay web server: an online tool to quantify translation-driven delays in protein native contact formation

Co-translational protein folding is shaped by the vectorial nature of translation, which causes residues to emerge sequentially from the ribosome. As a result, residues whose native interaction partners lie downstream in sequence cannot immediately form their native contacts and remain transiently unsatisfied until those partners are synthesized. These unsatisfied residues are vulnerable to non-native interactions and often require the engagement of co-translational chaperones. We previously developed the Native Fold Delay (NFD) metric to quantify the time lag between the synthesis of a residue and the point at which it can form all its native contacts. Here, we present the FoldDelay web server, a freely accessible platform that extends the NFD concept into a more comprehensive framework for analyzing native residue-residue contact formation during translation. Starting from user-submitted AlphaFold or PDB structures, the site identifies all N- to C-terminal residue-residue contacts, estimates their earliest possible formation times, and integrates domain annotations to distinguish between intra- and inter-domain contacts. The server provides a suite of linked interactive visualizations that allows users to explore native contact formation dynamics and detect transiently unsatisfied regions. The FoldDelay web server is freely accessible at https://folddelay.switchlab.org.