Limits...
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.

Show MeSH

Related in: MedlinePlus

EMatch flow. The strategy of EMatch consists of three stages. In the first stage, helices are identified in a given cryo-EM map of a protein complex. Their spatial arrangement is then used to query a data set of atomic resolution folds to find potential structural homologues of domains appearing in the map. In the final stage, which is currently under development, the potential atomic structural homologues of the domains are assembled into a quasi-model of the complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2483490&req=5

fig1: EMatch flow. The strategy of EMatch consists of three stages. In the first stage, helices are identified in a given cryo-EM map of a protein complex. Their spatial arrangement is then used to query a data set of atomic resolution folds to find potential structural homologues of domains appearing in the map. In the final stage, which is currently under development, the potential atomic structural homologues of the domains are assembled into a quasi-model of the complex.

Mentions: Here, we describe a new computational knowledge-based method, named EMatch, aimed at detecting a quasi-atomic structural model of a protein assembly for which a cryo-EM map at 6–10 Å resolution is available. Similar to the strategy suggested by Jiang et al. (2001 ▶), EMatch is a three-tier algorithm (see Fig. 1 ▶). Firstly, helices are identified in the given cryo-EM map. Their spatial arrangement is then used to query a data set of atomic resolution protein folds to find potential structural homologues of domains appearing in the map and their locations in the complex. The aim of the final stage, which is currently under development, is to assemble the potential atomic structural homologues of the domains into a quasi-model of the complex. An important novel contribution of the method is its ability to identify ‘partial alignments’ between the detected set of helices and the data-set folds. The method is capable of aligning structural homologous folds even if (i) only some of the helices of the folds are matched with helices in the cryo-EM map and/or (ii) the matched helices are not necessarily of exact length and orientation. Thus, the method is tolerant to noise in the cryo-EM map and capable of aligning structures that are not fully homologous to domains in the complex (for example, sequentially remote domains of the same fold). Another important strength of the method is its high efficiency, which makes the method applicable to both interpreting large complexes and querying a massive data set of possible folds.


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)

EMatch flow. The strategy of EMatch consists of three stages. In the first stage, helices are identified in a given cryo-EM map of a protein complex. Their spatial arrangement is then used to query a data set of atomic resolution folds to find potential structural homologues of domains appearing in the map. In the final stage, which is currently under development, the potential atomic structural homologues of the domains are assembled into a quasi-model of the complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: EMatch flow. The strategy of EMatch consists of three stages. In the first stage, helices are identified in a given cryo-EM map of a protein complex. Their spatial arrangement is then used to query a data set of atomic resolution folds to find potential structural homologues of domains appearing in the map. In the final stage, which is currently under development, the potential atomic structural homologues of the domains are assembled into a quasi-model of the complex.
Mentions: Here, we describe a new computational knowledge-based method, named EMatch, aimed at detecting a quasi-atomic structural model of a protein assembly for which a cryo-EM map at 6–10 Å resolution is available. Similar to the strategy suggested by Jiang et al. (2001 ▶), EMatch is a three-tier algorithm (see Fig. 1 ▶). Firstly, helices are identified in the given cryo-EM map. Their spatial arrangement is then used to query a data set of atomic resolution protein folds to find potential structural homologues of domains appearing in the map and their locations in the complex. The aim of the final stage, which is currently under development, is to assemble the potential atomic structural homologues of the domains into a quasi-model of the complex. An important novel contribution of the method is its ability to identify ‘partial alignments’ between the detected set of helices and the data-set folds. The method is capable of aligning structural homologous folds even if (i) only some of the helices of the folds are matched with helices in the cryo-EM map and/or (ii) the matched helices are not necessarily of exact length and orientation. Thus, the method is tolerant to noise in the cryo-EM map and capable of aligning structures that are not fully homologous to domains in the complex (for example, sequentially remote domains of the same fold). Another important strength of the method is its high efficiency, which makes the method applicable to both interpreting large complexes and querying a massive data set of possible folds.

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