ProStructLab: an open-access interactive platform for residue connectivity, structural communication, and topological perturbation analysis in proteins

Background Protein function depends not only on individual residues but also on their organization within structural interaction networks. However, many computational approaches for residue-network analysis require programming expertise, local installation, or fragmented workflows. ProStructLab was developed as an open-access, browser-based platform for interactive analysis of protein structures represented as residue-contact networks. Results ProStructLab integrates interactive three-dimensional visualization, residue selection, structural connectivity analysis, communication-hub identification, residue-set analysis, interaction pathways, Pathway Participation Score, and virtual residue knockout. The platform was benchmarked using 12 experimentally characterized protein systems representing catalytic residues, allosteric sites, and protein–protein interface hotspots. Communication Score distinguished catalytic residues from background residues with an area under the receiver operating characteristic curve of 0.786 and interface hotspots with a value of 0.862, whereas allosteric residues showed little global-centrality enrichment (0.454). Virtual residue knockout showed its strongest discriminatory performance for interface hotspots (0.857). Functional residue sets exhibited greater collective connectivity than size-matched random residue sets in all 11 systems evaluable for set analysis. In addition, three of four allosteric systems displayed significantly shorter mean network paths between regulatory and catalytic regions than randomized controls. Pathway Participation Score further identified recurrent structural intermediates connecting these functional regions. Conclusions ProStructLab provides an accessible framework for exploring complementary aspects of protein structural organization without requiring molecular dynamics simulations or advanced programming. The benchmark indicates that catalytic, allosteric, and interface residues exhibit distinct structural-network signatures, supporting the combined use of global-centrality, residue-set, pathway, and topological perturbation analyses for exploratory structural bioinformatics and hypothesis generation.