ANÁLISIS Y PREDICCIÓN DE ESTRUCTURA DE PROTEÍNAS. ESPECIALISTA EN BIOINFORMÁTICA. Madrid.  2003

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COMPARACIÓN SISTEMÁTICA DE ESTRUCTURA DE PROTEÍNAS.
Paulino Gómez-Puertas. CAB.

• Bases de datos de comparación de estructuras:
• SCOP
• The SCOP database, created by manual inspection and abetted by a battery of automated methods, aims to provide a detailed and comprehensive description of the structural and evolutionary relationships between all proteins whose structure is known.
 
• CATH
• CATH is a novel hierarchical classification of protein domain structures, which clusters proteins at four major levels, Class(C), Architecture(A), Topology(T) and Homologous superfamily (H).  Class, derived from secondary structure content, is assigned for more than 90% of protein structures automatically. Architecture, which describes the gross orientation of secondary structures, independent of connectivities, is currently assigned manually. The topology level clusters structures according to their toplogical connections and numbers of secondary structures. The homologous superfamilies cluster proteins with highly similar structures and functions. The assignments of structures to toplogy families and homologous superfamilies are made by sequence and structure comparisons

 
• FSSP (Dali)
• The Dali server is a network service for comparing protein structures in 3D. You submit the coordinates of a query protein structure and Dali compares them against those in the Protein Data Bank. A multiple alignment of structural neighbours is mailed back to you. In favourable cases, comparing 3D structures may reveal biologically interesting similarities that are not detectable by comparing sequences. If you want to know the structural neighbours of a protein already in the Protein Data Bank, you can find them in the FSSP database.
 
• Bases de datos relacionadas:
• HSSP (SRS)
• The HSSP database is a database of homology-derived secondary structure of proteins. It was designed by Chris Sander and Reinhard Schneider.

 
• DSSP (SRS)
• The DSSP program was designed by Wolfgang Kabsch and Chris Sander to standardize secondary structure assignment. The DSSP database is a database of secondary structure assignments (and much more) for all protein  entries in the Protein Data Bank (PDB)

 
• Uso del servidor Dali:
 
• Ejemplo: alineamiento estructural entre la chaperona hsc70 (pdb: 1hpm) y FtsA "atp-bound form" (pdb: 1e4g) <1hpm.pdb> <1e4g.pdb>
• Usar la página del servidor DALI
• Mensaje recibido: <mail_dali.html>
• La matriz de rotación-traslación (1e4g.pdb sobre 1hpm.pdb):
 
   2: 1924   mol2-T  U(1,.)   0.827668  0.114710  0.549370          -31.461958
   2: 1924   mol2-T  U(2,.)  -0.514832  0.544870  0.661865            1.270171
   2: 1924   mol2-T  U(3,.)  -0.223413 -0.830638  0.510028            7.714231
 
• Un truco: utilización del script: "matrixpdb.pl"
• El archivo 1e4g.pdb transformado: <1e4g.pdb.matrix>
• Juntar en un solo archivo 1hpm.pdb y 1e4g.pdb.matrix: <1e4g_1hpm_comp.pdb>
• Visualizarlo prestando atención a la localización del nucleótido.
 
• Otros ejercicios:
• Comparar estructuralmente:
• 2TCT vs 1NFN
• 9RNT vs 1AQZ

 
• Generar, usando Dalil y las entradas 1tub <1tub.pdb> y 1fsz <1fsz.pdb> de PDB, un modelo para la dimerización de FtsZ basado el el dímero de tubulina.

(ayuda: separar el archivo 1tub.pdb en dos archivos, uno para cada cadena. Obtener depués la matriz de rotación/traslación de 1fsz para cada una de las cadenas de tubulina)
 
• Generar, usando el mismo sistema, un modelo octamérico para una supuesta región apical formada por subunidades gamma de la chaperona CCT <1a6d_halfhexa.pdb>. Usar como molde la estructura del termosoma <1gml_A.pdb>.
 
• Comparar las estructuras <1gru_N.pdb> y <1gru_A.pdb>. ¿Por qué el alineamiento estructural no es bueno? Separar los diferentes dominios y compararlos entre sí.