Biomedical subjects

Dan Bolser

Publications and source records attributed to Dan Bolser.

4 recordsLinked to original sources

PubMed2005

Comparative interactomics analysis of protein family interaction networks using PSIMAP (protein structural interactome map).

MOTIVATION: Many genomes have been completely sequenced. However, detecting and analyzing their protein-protein interactions by experimental methods such as co-immunoprecipitation, tandem affinity purification and Y2H is not as fast as genome sequencing. Therefore, a computational prediction method based on the known protein structural interactions will be useful to analyze large-scale protein-protein interaction rules within and among complete genomes. RESULTS: We confirmed that all the predicted protein family interactomes (the full set of protein family interactions within a proteome) of 146 species are scale-free networks, and they share a small core network comprising 36 protein families related to indispensable cellular functions. We found two fundamental differences among prokaryotic and eukaryotic interactomes: (1) eukarya had significantly more hub families than archaea and bacteria and (2) certain special hub families determined the topology of the eukaryotic interactomes. Our comparative analysis suggests that a very small number of expansive protein families led to the evolution of interactomes and seemed to have played a key role in species diversification. SUPPLEMENTARY INFORMATION: http://interactomics.org.

Algorithms↗

PubMed2005

PSIbase: a database of Protein Structural Interactome map (PSIMAP).

UNLABELLED: Protein Structural Interactome map (PSIMAP) is a global interaction map that describes domain-domain and protein-protein interaction information for known Protein Data Bank structures. It calculates the Euclidean distance to determine interactions between possible pairs of structural domains in proteins. PSIbase is a database and file server for protein structural interaction information calculated by the PSIMAP algorithm. PSIbase also provides an easy-to-use protein domain assignment module, interaction navigation and visual tools. Users can retrieve possible interaction partners of their proteins of interests if a significant homology assignment is made with their query sequences. AVAILABILITY: http://psimap.org and http://psibase.kaist.ac.kr/

Binding Sites↗

PubMed2004

Using convex hulls to extract interaction interfaces from known structures.

MOTIVATION: Protein interactions provide an important context for the understanding of function. Experimental approaches have been complemented with computational ones, such as PSIMAP, which computes domain-domain interactions for all multi-domain and multi-chain proteins in the Protein Data Bank (PDB). PSIMAP has been used to determine that superfamilies occurring in many species have many interaction partners, to show examples of convergent evolution through shared interaction partners and to uncover complexes in the interaction map. To determine an interaction, the original PSIMAP algorithm checks all residue pairs of any domain pair defined by classification systems such as SCOP. The computation takes several days for the PDB. The computation of PSIMAP has two shortcomings: first, the original PSIMAP algorithm considers only interactions of residue pairs rather than atom pairs losing information for detailed analysis of contact patterns. At the atomic level the original algorithm would take months. Second, with the superlinear growth of PDB, PSIMAP is not sustainable. RESULTS: We address these two shortcomings by developing a family of new algorithms for the computation of domain-domain interactions based on the idea of bounding shapes, which are used to prune the search space. The best of the algorithms improves on the old PSIMAP algorithm by a factor of 60 on the PDB. Additionally, the algorithms allow a distributed computation, which we carry out on a farm of 80 Linux PCs. Overall, the new algorithms reduce the computation at atomic level from months to 20 min. The combination of pruning and distribution makes the new algorithm scalable and sustainable even with the superlinear growth in PDB.

Algorithms↗

PubMed2003

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome.

BACKGROUND: Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. RESULTS: We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. CONCLUSIONS: Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

Archaeal Proteins↗