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EMatch: an efficient method for aligning atomic resolution subunits into intermediate-resolution cryo-EM maps of large macromolecular assemblies.

Dror O, Lasker K, Nussinov R, Wolfson H - Acta Crystallogr. D Biol. Crystallogr. (2006)

Bottom Line: Structural analysis of biological machines is essential for inferring their function and mechanism.Nevertheless, owing to their large size and instability, deciphering the atomic structure of macromolecular assemblies is still considered as a challenging task that cannot keep up with the rapid advances in the protein-identification process.The method recognizes and locates possible atomic resolution structural homologues of protein domains in the assembly.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel. oranit@post.tau.ac.il

ABSTRACT
Structural analysis of biological machines is essential for inferring their function and mechanism. Nevertheless, owing to their large size and instability, deciphering the atomic structure of macromolecular assemblies is still considered as a challenging task that cannot keep up with the rapid advances in the protein-identification process. In contrast, structural data at lower resolution is becoming more and more available owing to recent advances in cryo-electron microscopy (cryo-EM) techniques. Once a cryo-EM map is acquired, one of the basic questions asked is what are the folds of the components in the assembly and what is their configuration. Here, a novel knowledge-based computational method, named EMatch, towards tackling this task for cryo-EM maps at 6-10 A resolution is presented. The method recognizes and locates possible atomic resolution structural homologues of protein domains in the assembly. The strengths of EMatch are demonstrated on a cryo-EM map of native GroEL at 6 A resolution.

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Related in: MedlinePlus

Evaluation of a priori unknown domain reconstruction. (a) The SCOP superfamily representative for the equatorial domain (red) superimposed by EMatch on the cryo-EM map (not shown) and the same structure (grey) superimposed by MASS on the atomic quasi-structural model constructed in the first experiment. (b) and (c) Similar figures for the apical (yellow) and intermediate (blue) domains, respectively.
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fig4: Evaluation of a priori unknown domain reconstruction. (a) The SCOP superfamily representative for the equatorial domain (red) superimposed by EMatch on the cryo-EM map (not shown) and the same structure (grey) superimposed by MASS on the atomic quasi-structural model constructed in the first experiment. (b) and (c) Similar figures for the apical (yellow) and intermediate (blue) domains, respectively.

Mentions: The top-ranking alignment for the SCOP superfamily representative of the equatorial domain contains six matched helices with an r.m.s.d. of 3.50 Å between their axial midpoints. For the superfamily representative of the apical domain, the top-ranking alignment consists of three matched helices with an r.m.s.d. of 1.20 Å between their axial midpoints. Finally, the top-ranking alignment for the superfamily representative of the intermediate domain contains three matched helices with an r.m.s.d. of 3.20 Å between their axial midpoints. For all the three superfamily representatives, the top-ranking alignment has achieved an evaluation r.m.s.d. lower than 7 Å, namely 1.07, 6.33 and 6.65 Å for the equatorial, apical and intermediate domains, respectively. The evaluation r.m.s.d. for the whole constructed complex is 4.76 Å. Further details of the alignments (including Z scores and additional data on the matched helices) are available in Table 3 ▶, Fig. 4 ▶ and the website. The results clearly demonstrate the potential of EMatch to detect alignments that are almost as accurate as atomic based ones. This success in bridging the resolution gap is achieved by the capability of EMatch to extract sufficient secondary-structure information from the cryo-EM maps and to find partial alignments between the SSEs and the high-resolution structures.


EMatch: an efficient method for aligning atomic resolution subunits into intermediate-resolution cryo-EM maps of large macromolecular assemblies.

Dror O, Lasker K, Nussinov R, Wolfson H - Acta Crystallogr. D Biol. Crystallogr. (2006)

Evaluation of a priori unknown domain reconstruction. (a) The SCOP superfamily representative for the equatorial domain (red) superimposed by EMatch on the cryo-EM map (not shown) and the same structure (grey) superimposed by MASS on the atomic quasi-structural model constructed in the first experiment. (b) and (c) Similar figures for the apical (yellow) and intermediate (blue) domains, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483490&req=5

fig4: Evaluation of a priori unknown domain reconstruction. (a) The SCOP superfamily representative for the equatorial domain (red) superimposed by EMatch on the cryo-EM map (not shown) and the same structure (grey) superimposed by MASS on the atomic quasi-structural model constructed in the first experiment. (b) and (c) Similar figures for the apical (yellow) and intermediate (blue) domains, respectively.
Mentions: The top-ranking alignment for the SCOP superfamily representative of the equatorial domain contains six matched helices with an r.m.s.d. of 3.50 Å between their axial midpoints. For the superfamily representative of the apical domain, the top-ranking alignment consists of three matched helices with an r.m.s.d. of 1.20 Å between their axial midpoints. Finally, the top-ranking alignment for the superfamily representative of the intermediate domain contains three matched helices with an r.m.s.d. of 3.20 Å between their axial midpoints. For all the three superfamily representatives, the top-ranking alignment has achieved an evaluation r.m.s.d. lower than 7 Å, namely 1.07, 6.33 and 6.65 Å for the equatorial, apical and intermediate domains, respectively. The evaluation r.m.s.d. for the whole constructed complex is 4.76 Å. Further details of the alignments (including Z scores and additional data on the matched helices) are available in Table 3 ▶, Fig. 4 ▶ and the website. The results clearly demonstrate the potential of EMatch to detect alignments that are almost as accurate as atomic based ones. This success in bridging the resolution gap is achieved by the capability of EMatch to extract sufficient secondary-structure information from the cryo-EM maps and to find partial alignments between the SSEs and the high-resolution structures.

Bottom Line: Structural analysis of biological machines is essential for inferring their function and mechanism.Nevertheless, owing to their large size and instability, deciphering the atomic structure of macromolecular assemblies is still considered as a challenging task that cannot keep up with the rapid advances in the protein-identification process.The method recognizes and locates possible atomic resolution structural homologues of protein domains in the assembly.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel. oranit@post.tau.ac.il

ABSTRACT
Structural analysis of biological machines is essential for inferring their function and mechanism. Nevertheless, owing to their large size and instability, deciphering the atomic structure of macromolecular assemblies is still considered as a challenging task that cannot keep up with the rapid advances in the protein-identification process. In contrast, structural data at lower resolution is becoming more and more available owing to recent advances in cryo-electron microscopy (cryo-EM) techniques. Once a cryo-EM map is acquired, one of the basic questions asked is what are the folds of the components in the assembly and what is their configuration. Here, a novel knowledge-based computational method, named EMatch, towards tackling this task for cryo-EM maps at 6-10 A resolution is presented. The method recognizes and locates possible atomic resolution structural homologues of protein domains in the assembly. The strengths of EMatch are demonstrated on a cryo-EM map of native GroEL at 6 A resolution.

Show MeSH
Related in: MedlinePlus