Biomedical subjects

Pedro Lopez-Romero

Publications and source records attributed to Pedro Lopez-Romero.

4 recordsLinked to original sources

PubMed2006

TreeDet: a web server to explore sequence space.

The TreeDet (Tree Determinant) Server is the first release of a system designed to integrate results from methods that predict functional sites in protein families. These methods take into account the relation between sequence conservation and evolutionary importance. TreeDet fully analyses the space of protein sequences in either user-uploaded or automatically generated multiple sequence alignments. The methods implemented in the server represent three main classes of methods for the detection of family-dependent conserved positions, a tree-based method, a correlation based method and a method that employs a principal component analyses coupled to a cluster algorithm. An additional method is provided to highlight the reliability of the position in the alignments. The server is available at http://www.pdg.cnb.uam.es/servers/treedet.

Amino Acid Sequence↗

PubMed2006

Computational approaches to model ligand selectivity in drug design.

To be effective, a designed drug must discriminate successfully the macromolecular target from alternative structures present in the organism. The last few years have witnessed the emergence of different computational tools aimed to the understanding and modeling of this process at molecular level. Although still rudimentary, these methods are shaping a coherent approach to help in the design of molecules with high affinity and specificity, both in lead discovery and in lead optimization. It is the purpose of this review to illustrate the array of computational tools available to consider selectivity in the design process, to summarize the most relevant applications, and to sketch the challenges ahead.

Amino Acid Sequence↗

PubMed2005

Core deformations in protein families: a physical perspective.

An analysis is presented on how structural cores change shape within protein families, and whether or not there is a relationship between these structural changes and the vibrational modes that proteins experiment due to topological constraints. A set of 13 representative and well-populated protein families are studied. The evolutionary directions of deformation are obtained by applying a new multiple structural alignment technique to superimpose the structures and extract a conserved core, together with Principal Components Analysis (PCA) to extract the main deformation modes. A low-resolution Normal Mode Analysis (NMA) technique is used in parallel to study the properties of the mechanical core plasticity of the same proteins. We find that the evolutionary deformations span a low dimensional space. A statistically significant correspondence exists between these principal deformations and the vibrational modes accessible to a particular topology. We conclude that, to a significant extent, the structures of evolving proteins seem to respond to sequence changes by collective deformations along combinations of low-frequency modes. The findings have implications in structure prediction by homology modeling.

Chemical Phenomena↗

PubMed2004

An analysis of core deformations in protein superfamilies.

An analysis is presented on how structural cores modify their shape across homologous proteins, and whether or not a relationship exists between these structural changes and the vibrational normal modes that proteins experience as a result of the topological constraints imposed by the fold. A set of 35 representative, well-populated protein families is studied. The evolutionary directions of deformation are obtained by using multiple structural alignments to superimpose the structures and extract a conserved core, together with principal components analysis to extract the main deformation modes from the three-dimensional superimposition. In parallel, a low-resolution normal mode analysis technique is employed to study the properties of the mechanical core plasticity of these same families. We show that the evolutionary deformations span a low dimensional space of 4-5 dimensions on average. A statistically significant correspondence exists between these principal deformations and the approximately 20 slowest vibrational modes accessible to a particular topology. We conclude that, to a significant extent, the structural response of a protein topology to sequence changes takes place by means of collective deformations along combinations of a small number of low-frequency modes. The findings have implications in structure prediction by homology modeling.

Amino Acid Sequence↗