MASS and MultiProt methods

Problem DefinitionProblem DefinitionInput: a collection of 3D protein structures

Goal: find substructures common to two or more proteins

The problem is complicated due to:- Similar substructures instead of identical

- Partial alignments (smaller common substructures)

- Subset alignments

A A

B B

A

BC

C

Common substructures:

P1 P2 P3

A B C

MultiProt MASS

Algorithm Considers all structures simultaneously

Based on contiguous fragments

Based on secondary structures

Applications Subset structural core detection

Sequential as well as non-sequential alignment

Fine structural core detection

Fast fold detection

MultiProt and MASS

• Ensemble: 10 proteins from 4 different folds and 6 different superfamilies in SCOP

• Runtime: 48 seconds• Core: 4-helical bundle

Non-Topological AlignmentNon-Topological AlignmentHelix-Bundle EnsembleHelix-Bundle Ensemble

P: Q:

Classification of DNA-Binding ProteinsClassification of DNA-Binding Proteins

The ensemble contains 18 DNA-binding proteins that can be classified into 5 structural classes:– Classic zinc finger (7 molecules)– Histones (3 molecules)– Phage repressors (3 molecules)– Restriction endonuclease-like (3 molecules)– Winged helix (3 molecules).

Subset AlignmentsSubset Alignments

A. Zinc Finger

D. Restriction endonuclease-like E. Winged Helix

C. Phage repressorsB. Histones

- DNA

The ensemble contains 12 sequentially non-redundant structures taken from the two families of the Actin depolymerizing proteins fold:− Cofilin-like (CL) family (4 molecules)

− Gelsolin-like (GL) family (8 molecules)

Cofilin-like and Gelsolin-like FamiliesCofilin-like and Gelsolin-like FamiliesSubset Alignments (cont.)Subset Alignments (cont.)

A. Alignment of all 12 proteins

B. Alignment of all 8 GL proteins

C. Alignment of all 4 CL proteins

D. Alignment of 3 CL proteins

PDB:1f7s lacks this helix

28 residues RMSD 1.9

63 residues RMSD 1.5

104 residues RMSD 1.2

120 residues RMSD 1.3

Detection of Two Common MotifsDetection of Two Common Motifs

46 residuesRMSD 1.7

45 residuesRMSD 1.6

- DNA of PDB:1cgpA- DNA of PDB:1ddnA-DNA of PDB:1fokA

A

Winged-helix proteins

B

AB

PTB phosphotyrosine-binding domains[binding diversity]

Recognition of conserved core of PLP dependent transferase for focused

docking