BioAssemblyModeler (BAM): user-friendly homology modeling of protein homo- and heterooligomers

Abstract

Many if not most proteins function in oligomeric assemblies of one or more protein sequences. The Protein Data Bank provides coordinates for biological assemblies for each entry, at least 60% of which are dimers or larger assemblies. BioAssemblyModeler (BAM) is a graphical user interface to the basic steps in homology modeling of protein homooligomers and heterooligomers from the biological assemblies provided in the PDB. BAM takes as input up to six different protein sequences and begins by assigning Pfam domains to the target sequences. The program utilizes a complete assignment of Pfam domains to sequences in the PDB, PDBfam (http://dunbrack2.fccc.edu/protcid/pdbfam), to obtain templates that contain any or all of the domains assigned to the target sequence(s). The contents of the biological assemblies of potential templates are provided, and alignments of the target sequences to the templates are produced with a profile-profile alignment algorithm. BAM provides for visual examination and mouse-editing of the alignments supported by target and template secondary structure information and a 3D viewer of the template biological assembly. Side-chain coordinates for a model of the biological assembly are built with the program SCWRL4. A built-in protocol navigation system guides the user through all stages of homology modeling from input sequences to a three-dimensional model of the target complex.

Availability: http://dunbrack.fccc.edu/BAM.

Figure 1. Screenshot of BAM showing a modeling session of a heterohexameric complex.

For details, please refer to Results and Discussion section.

Figure 2. Minimum sequence identity within Pfam domain families identified in PDB structures with PDBfam.

Kernel density estimates of the minimum sequence identifies are shown for a total of 3730 Pfams. The sequence identities were determined by alignment of pairs of PDB sequences to the same HMM (curve labeled HMM) or by structure alignment with the program FATCAT.

Figure 3. Minimum sequence identities in ProtCID clusters of common interfaces between identical Pfams (A) or different Pfams (B).

The minimum sequence identity for each pair of domains in the same interface cluster using both FATCAT and transitive alignment via the Pfam HMM(s). For Pfam pairs, the minimum of the two Pfams was used in the density estimate. Same-Pfam clusters may contain homodimers and/or heterodimers that belong to the same Pfam domain family.