A framework for computational and experimental methods: identifying dimerization residues in CCR chemokine receptors.

in Bioinformatics (2005), 21 Suppl 2

Solving relevant biological problems requires answering complex questions. Addressing such questions traditionally implied the design of time-consuming experimental procedures which most of the time are ... [more ▼]

Solving relevant biological problems requires answering complex questions. Addressing such questions traditionally implied the design of time-consuming experimental procedures which most of the time are not accessible to average-sized laboratories. The current trend is to move towards a multidisciplinary approach integrating both theoretical knowledge and experimental work. This combination creates a powerful tool for shedding light on biological problems. To illustrate this concept, we present here a descriptive example of where computational methods were shown to be a key aspect in detecting crucial players in an important biological problem: the dimerization of chemokine receptors. Using evolutionary based sequence analysis in combination with structural predictions two CCR5 residues were selected as important for dimerization and further validated experimentally. The experimental validation of computational procedures demonstrated here provides a wealth of valuable information not obtainable by any of the individual approaches alone. [less ▲]

Topology of small-world networks of protein-protein complex structures.

in Bioinformatics (2005), 21(8), 1311-5

The majority of real examples of small-world networks exhibit a power law distribution of edges among the nodes, therefore not fitting into the wiring model proposed by Watts and Strogatz. However ... [more ▼]

The majority of real examples of small-world networks exhibit a power law distribution of edges among the nodes, therefore not fitting into the wiring model proposed by Watts and Strogatz. However, protein structures can be modeled as small-world networks, with a distribution of the number of links decaying exponentially as in the case of this wiring model. We approach the protein-protein interaction mechanism by viewing it as a particular rewiring occurring in the system of two small-world networks represented by the monomers, where a re-arrangement of links takes place upon dimerization leaving the small-world character in the dimer network. Due to this rewiring, the most central residues at the complex interfaces tend to form clusters, which are not homogenously distributed. We show that these highly central residues are strongly correlated with the presence of hot spots of binding free energy. CONTACT: ao-mesa@fujirebio.co.jp SUPPLEMENTARY INFORMATION: http://www.fujirebio.co.jp/support/index.php (under construction). [less ▲]

Automatic methods for predicting functionally important residues.

in Journal of molecular biology (2003), 326(4), 1289-302

Sequence analysis is often the first guide for the prediction of residues in a protein family that may have functional significance. A few methods have been proposed which use the division of protein ... [more ▼]

Sequence analysis is often the first guide for the prediction of residues in a protein family that may have functional significance. A few methods have been proposed which use the division of protein families into subfamilies in the search for those positions that could have some functional significance for the whole family, but at the same time which exhibit the specificity of each subfamily ("Tree-determinant residues"). However, there are still many unsolved questions like the best division of a protein family into subfamilies, or the accurate detection of sequence variation patterns characteristic of different subfamilies. Here we present a systematic study in a significant number of protein families, testing the statistical meaning of the Tree-determinant residues predicted by three different methods that represent the range of available approaches. The first method takes as a starting point a phylogenetic representation of a protein family and, following the principle of Relative Entropy from Information Theory, automatically searches for the optimal division of the family into subfamilies. The second method looks for positions whose mutational behavior is reminiscent of the mutational behavior of the full-length proteins, by directly comparing the corresponding distance matrices. The third method is an automation of the analysis of distribution of sequences and amino acid positions in the corresponding multidimensional spaces using a vector-based principal component analysis. These three methods have been tested on two non-redundant lists of protein families: one composed by proteins that bind a variety of ligand groups, and the other composed by proteins with annotated functionally relevant sites. In most cases, the residues predicted by the three methods show a clear tendency to be close to bound ligands of biological relevance and to those amino acids described as participants in key aspects of protein function. These three automatic methods provide a wide range of possibilities for biologists to analyze their families of interest, in a similar way to the one presented here for the family of proteins related with ras-p21. [less ▲]

Connection between type A and E factorizations and construction of satellite algebras

in Journal of Physics: A Mathematical and General (2000)

Generalized Morse potential: Symmetry and satellite potentials

in Journal of Physics: A Mathematical and General (1998)

Supermultiplicity and the relativistic coulomb problem with arbitrary spin

in Foundations of Physics (1997)

On some solutions of the Dirac equation

in Journal of Physics: A Mathematical and General (1996)

Symmetry Lie algebra of the two body systems with a Dirac oscillator interaction

in Revista Mexicana de Física (1995)

Relationship between different approaches to the relativistic two body problem

in Journal of Physics: A Mathematical and General (1994)

Transformation from U(3) to a pseudo U(3) basis of the matrix representation of a deformed Nilsson hamiltonian

in Revista Mexicana de Física (1992)