Fig. 3: Comparing the performances of MELO and avaiable methods in measuring structural variation.
From: Measuring and locating the changes in protein structure using MELO
a comparing the accuracies of two methods across four SCOP2 classification levels (Class, Fold/IUPR, Superfamily, and Family). MELO maintained a consistent accuracy >99.9% at all levels, providing greater precision than TM-score in identifying the change at the level of superfamily and family (increased by about 5%). b accuracy assessments between MELO and TM-score in identifying structural change induced by relatively small sequence alterations (the protein pairs with sequence identity >70%). MELO kept consistent accuracy above 99.9% at all levels, substantially outperforming TM-score. c the assignments of two million structure pairs (sequence identity >70%) into four Quadrants (Q1 to Q4) based on the results of VSSmeasur and SPSmeasur. The pie charts provided the level of agreement between MELO and TM-score in each Quadrant. In Q1, the MELO and TM-score mostly achieved the same conclusions with 0.01% disagreement. In Q2, Q3 and Q4, where MELO found structure changes, the findings of two methods were largely inconsistent, with 86.45%, 97.23% and 91.95% pairs having distinct conclusion, respectively. d a representative pair of proteins in Q2 (Borrelia burgdorferi OspA before and after the replacement of two β-hairpin sequences with Gly-Gly and shortening of one β-hairpin). Shifts among protein segments were captured by MELO (VSSmeasur = 0.13, SPSmeasur = 0.63), while both TM-score and LDDT failed to identify these structural changes. e a representative protein pair in Q3 (intestinal fatty acid-binding protein and its helix-less variant). Both the variations in secondary structures and shifts among protein segments were successfully identified by MELO (VSSmeasur = 0.66 & SPSmeasur = 0.65), but not found by TM-score and RMSD. f a representative protein pair in Q4 (change of some ordered secondary structures to disordered ones in SARS-CoV-2 spike protein induced by multi-point mutations). Such changes were successfully captured by MELO (VSSmeasur = 0.56 & SPSmeasur = 0.35), but did not discovered by other existing methods.
