Contact Lens: Evaluating Protein Structure by Contacts

1. Contact Lens: Evaluating Protein Structure by Contacts GDT vs. Contact Lens The Global Distance Test is a measure of the number of residues whose distance between two superimposed structures is less than a certain threshold. Because GDT requires multiple super-positions it is computationally expensive. Two predicted structures of T0203 (red), superimposed upon the native structure (blue PDB:1vkpA, 382 residues). The “align2” model on the left is the top scorer for Contact Lens, while “model5” had the best RMSD score. While both models show many secondary structure similarities, model5 is overly compact. When Contact Lens is plotted against GDT the two scores often trend together across the whole range, yet show great differences in a local area. T0274 (red), superimposed on native (PDB: 1wgb 159 residues). Both models closely match most of 11 beta and 3 helices. However, while GDT scores these identically, Contact Lens scores the left figure higher. The model on the right has a prominent unaligned loop, which may account for some of this difference. Two graphs of Contact Lens vs RMSD. While the two scores frequently show a similar trend as seen on the left, it may be the differences that tell the story. Tim Dreszer -University of California at Santa Cruz Rapid evaluation of the similarity of two structures is an essential tool in protein 3D structure prediction. Perhaps the most widely used tool is RMSD, yet it suffers several major shortcomings. Another is GDT (as used in CASP6), however it is computationally expensive and still comes up short. In this project a new tool is developed based upon residue-residue contacts. While the basic contact score has strengths, it is improved upon by rewarding distant contacts and near identical contact distances, as well as smoothing the boundary at the contact threshold and normalizing the score. This contact measure dubbed “contact lens” is used to evaluate CASP6 structure predictions. Contact lens proves better than both RMSD and GDT at resolving some structure similarities. RMSD vs. Contact Lens Root Mean Square Distance is a measure of the distance between the same residue in two different structures that have been superimposed. While it is easy to calculate, it fails to recognize overly compact structures and allows small discrepancies to overwhelm the score. A traditional contact measure is a count of intra-chain Cα pairs that are within a certain threshold distance of each other, as compared with the expected contacts in the native structure. Conclusions Contact lens shows strong localized differences from both RMSD and GDT, yet trends with each of them across the scoring range. The advantages of Contact Lens over GDT appear most obvious, as computation is significantly reduced and intra-model consistencies are rewarded. In almost all cases where GDT and Contact Lens disagreed, RMSD agreed with Contact Lens. Like RMSD, the current form of contact lens may be overly sensitive to global folding, at the expense of secondary structure. Fortunately, this tool is easily recalibrated for near or far-sightedness. Acknowledgements:Kevin Karplus, fellow students of BME220 and the many contributors to protein structure prediction methods at UCSC.