Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

Original languageEnglish (US)
Pages (from-to)e0154786
JournalPLoS One
Volume11
Issue number5
DOIs
StatePublished - 2016

Fingerprint

Uncertainty
uncertainty
X-Rays
X-radiation
X rays
Nuclear magnetic resonance
testing
Uncertainty analysis
uncertainty analysis
prediction
Crystal lattices
Caspase 3
protein structure
Magnetic Resonance Spectroscopy
Servers
space and time
crystals
nuclear magnetic resonance spectroscopy
Proteins
Experiments

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models. / Li, Wenlin; Schaeffer, R. Dustin; Otwinowski, Zbyszek; Grishin, Nick V.

In: PLoS One, Vol. 11, No. 5, 2016, p. e0154786.

Research output: Contribution to journalArticle

@article{2ec2578633a84b5e9fbaa5bda8b5168a,
title = "Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models",
abstract = "The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.",
author = "Wenlin Li and Schaeffer, {R. Dustin} and Zbyszek Otwinowski and Grishin, {Nick V.}",
year = "2016",
doi = "10.1371/journal.pone.0154786",
language = "English (US)",
volume = "11",
pages = "e0154786",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models

AU - Li, Wenlin

AU - Schaeffer, R. Dustin

AU - Otwinowski, Zbyszek

AU - Grishin, Nick V.

PY - 2016

Y1 - 2016

N2 - The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

AB - The Critical Assessment of techniques for protein Structure Prediction (or CASP) is a community-wide blind test experiment to reveal the best accomplishments of structure modeling. Assessors have been using the Global Distance Test (GDT_TS) measure to quantify prediction performance since CASP3 in 1998. However, identifying significant score differences between close models is difficult because of the lack of uncertainty estimations for this measure. Here, we utilized the atomic fluctuations caused by structure flexibility to estimate the uncertainty of GDT_TS scores. Structures determined by nuclear magnetic resonance are deposited as ensembles of alternative conformers that reflect the structural flexibility, whereas standard X-ray refinement produces the static structure averaged over time and space for the dynamic ensembles. To recapitulate the structural heterogeneous ensemble in the crystal lattice, we performed time-averaged refinement for X-ray datasets to generate structural ensembles for our GDT_TS uncertainty analysis. Using those generated ensembles, our study demonstrates that the time-averaged refinements produced structure ensembles with better agreement with the experimental datasets than the averaged X-ray structures with B-factors. The uncertainty of the GDT_TS scores, quantified by their standard deviations (SDs), increases for scores lower than 50 and 70, with maximum SDs of 0.3 and 1.23 for X-ray and NMR structures, respectively. We also applied our procedure to the high accuracy version of GDT-based score and produced similar results with slightly higher SDs. To facilitate score comparisons by the community, we developed a user-friendly web server that produces structure ensembles for NMR and X-ray structures and is accessible at http://prodata.swmed.edu/SEnCS. Our work helps to identify the significance of GDT_TS score differences, as well as to provide structure ensembles for estimating SDs of any scores.

UR - http://www.scopus.com/inward/record.url?scp=85014084261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014084261&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0154786

DO - 10.1371/journal.pone.0154786

M3 - Article

VL - 11

SP - e0154786

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

ER -