Global distance test

The global distance test (GDT), also written as GDT_TS to represent "total score", is a measure of similarity between two protein structures with known amino acid correspondences (e.g. identical amino acid sequences) but different tertiary structures. It is most commonly used to compare the results of protein structure prediction to the experimentally determined structure as measured by X-ray crystallography, protein NMR, or, increasingly, cryoelectron microscopy.

The GDT metric was developed by Adam Zemla at Lawrence Livermore National Laboratory and originally implemented in the Local-Global Alignment (LGA) program.[1][2] It is intended as a more accurate measurement than the common root-mean-square deviation (RMSD) metric - which is sensitive to outlier regions created, for example, by poor modeling of individual loop regions in a structure that is otherwise reasonably accurate.[1] The conventional GDT_TS score is computed over the alpha carbon atoms and is reported as a percentage, ranging from 0 to 100. In general, the higher the GDT_TS score, the more closely a model approximates a given reference structure.

GDT_TS measurements are used as major assessment criteria in the production of results from the Critical Assessment of Structure Prediction (CASP), a large-scale experiment in the structure prediction community dedicated to assessing current modeling techniques.[1][3][4] The metric was first introduced as an evaluation standard in the third iteration of the biannual experiment (CASP3) in 1998.[3] Various extensions to the original method have been developed; variations that accounts for the positions of the side chains are known as global distance calculations (GDC).[5]

  1. ^ a b c Zemla A (2003). "LGA: A method for finding 3D similarities in protein structures". Nucleic Acids Research. 31 (13): 3370–3374. doi:10.1093/nar/gkg571. PMC 168977. PMID 12824330.
  2. ^ US patent 8024127 B2, Adam Zemla, "Local-Global Alignment for Finding 3D Similarities in Protein Structures", issued 20 September 2011, assigned to Lawrence Livermore National Security, LLC 
  3. ^ a b Zemla A, Venclovas C, Moult J, Fidelis K (1999). "Processing and analysis of CASP3 protein structure predictions". Proteins. S3 (S3): 22–29. doi:10.1002/(SICI)1097-0134(1999)37:3+<22::AID-PROT5>3.0.CO;2-W. PMID 10526349. S2CID 29803757.
  4. ^ Zemla A, Venclovas C, Moult J, Fidelis K (2001). "Processing and evaluation of predictions in CASP4". Proteins. 45 (S5): 13–21. doi:10.1002/prot.10052. PMID 11835478. S2CID 28166260.
  5. ^ Keedy, D.A.; Williams, CJ; Headd, JJ; Arendall, WB; Chen, VB; Kapral, GJ; Gillespie, RA; Block, JN; Zemla, A; Richardson, DC; Richardson, JS (2009). "The other 90% of the protein: Assessment beyond the α-carbon for CASP8 template-based and high-accuracy models". Proteins. 77 (Suppl 9): 29–49. doi:10.1002/prot.22551. PMC 2877634. PMID 19731372.