Life Sciences

Overview: 

The research program integrates different independent research leaded by senior scientists who work in different aspects of computational biology, ranging from bioinformatics for genomics to computational biochemistry. The program is originated as a collaborative effort with other institutions like ICREA, IRB-PCB-UB and the National Institute of Bioinformatics.

LIFE SCIENCES DEPARTMENT DIRECTOR

Orozco López, Modesto

NEWS

PCA suite: Software package for lossy trajectory compression using Principal Component Analysis (PCA) techniques.

The first dynamic map of proteins revealed. The MMB group has determined the first dynamic map of protein movements by determining trajectories of protein metafolds in aqueous solution using four different force-fields. Results have been recently published in Proc. Natl. Acad. Sci. USA. (2007) 104, 796-801.

Objectives: 

Our main goal is to gain a deep insight into the origin, evolution and function of living organisms using theory and computation. Our focus goes from a global analysis of living entities understood as complex systems to detailed studies of key interactions at the sub-atomic level. Overall, our objective is to make theory and simulation as one of the driving forces to the advance of research in life sciences.

Research Lines: 
The fundamental goal of our group is the theoretical study of biochemical systems, from general methodological development, to the analysis of specific problems of special biological relevance. For instance, we are using molecular dynamics and statistical mechanics to study anomalous forms of nucleic acids. Particular attention is paid to the study of conformational transitions in DNA, drug-DNA interactions, and the analysis of triple helices and other structures of potential impact in antigene or antisense therapies. We are also interested in the understanding of the basis of protein interactions, including those of pharmacological importance, and have also made several studies on very basic aspects of enzymatic reactivity, protein folding and docking. In this context, we have created the MODEL (Molecular Dynamics Extended Library) library of molecular dynamics trajectories for all the representative proteins. The project, the largest of this type in the world, provide us with a complete picture of protein dynamics and help us in drug-design projects.
 
Our goal is to take advantage of computing resources to contribute to the general understanding of the biology of genomes. We are focused in the design, development, and use of bioinformatic protocols and tools in the context of comparative genomics and analyses of gene and protein collections. These approaches are designed to answer questions related to the modifications of genes and regulatory regions during evolution and their impact in the physiology of the organisms, as well as to understand the evolution of biological systems.

The key aim of the INB is to generate and apply bioinformatics solutions to special requirements emerging from the development and execution of national research projects with a genomic or proteomics focus. Within INB the mission Computational Node 2 is to provide computational resources, including hardware specifically intended to the INB, biological databases, and generic analysis applications to the bioinformatics community.

Our research focuses on theoretical and computational approaches to protein interactions. We aim to develop and optimize computational algorithms for characterizing and understanding protein-protein association, which remains one of the most important challenges in Structural Biology. The ultimate goal is to understand the subtle determinants of the specificity of protein-protein binding, which in turn will help us to make more accurate predictions of complexes of biological and therapeutical interest. All this knowledge will also help to predict the interaction of small molecules with protein-protein interfaces, with the goal of designing compounds capable of inhibiting protein interactions of therapeutical interest.

  • ELECTRONIC AND ATOMIC PROTEIN MODELLING
    Victor Guallar

    Our main goal is the study of complex biochemical processes both at an electronic, by means of quantum mechanics, and atomic, by means of classical mechanics, theoretical detail. First, we place particular on the application of such methods, with emphasis on protein-ligand interactions. The second area involves the development of new methodological components, centered in obtaining long time protein dynamics by means of a kinetic Monte Carlo scheme.

SELECTED PUBLICATIONS

M.Rueda, C.Ferrer, T.Meyer, A.Pérez, J.Camps, A.Hospital, J.L.Gelpí and M.Orozco. A consensus view of protein dynamics. Proc. Natl. Acad. Sci. USA. 104, 796-801. January 2007

Suyama M, Harrington E, Bork P, Torrents D. Identification and analysis of genes and pseudogenes within duplicated regions in the human and mouse genomes. PLoS Comput Biol. 30; 2(6):e76, June 2006.

Guallar V, Jarzecki A, Friesner RA., Spiro TG. Modeling of Ligation-Induced Helix/Loop Displacements in Myoglobin; Toward an Understanding of Hemoglobin in Allostery. J. Am. Chem. Soc., 129, 5427-5435, April 2006.

Chelliah V, Blundell TL, Fernández-Recio, J. Efficient Restraints for Protein-Protein Docking by Comparison of Observed Amino Acid Substitution Patterns with those Predicted from Local Environment. J. Mol. Biol. 357, 1669-1682, April 2006.

Rueda M, Luque FJ, Orozco M. G-DNA can maintain its structure in the gas phase. J. Am. Chem. Soc., 128, 3609-3619, March 2006.

Federici L, Di Matteo A, Fernández-Recio J, Tsernoglou D, Cervone F. Polygalacturonase inhibiting proteins: players in plant innate immunity? Trends Plant Sci. 11, 65-70, February 2006.

Chimpanzee Sequencing and Analysis Consortium (including D. Torrents). Initial sequence of the chimpanzee genome and comparison with the human genome. Nature.;437(7055):69-87, September 2005.

Ferrer-Costa C. Gelpí JL, Zamacola L, Párraga I, de la Cruz X, Orozco M. PMUT: a web-based tool for the annotation of pathological mutations on proteins Bioinformatics, 21, 3176-3178, 15 July 2005.

Noy A, Pérez A, Marquez M, Luque FJ, Orozco M. Structure, recognition properties, and flexibility of the DNA.RNA hybrid. J. Am. Chem. Soc., 127, 4901-4920, 6 April 2005.

Crespo A, Martí MA, Kalko SG, Morreale A, Orozco M, Gelpí JL, Luque FJ. Theoretical study of the truncated hemoglobin HbN: exploring the molecular basis of the NO detoxification mechanism Theoretical study of the truncated hemoglob J. Am. Chem. Soc., 127, 4433-4444, 30 March 2005.

Guallar V, Borrelli KP. A Novel Binding Mechanism in Protein-Nucleotide Interaction: Implication for U1A RNA binding. Proc. Natl. Acad. of Science, 102,3954-3959, March 2005.

PEOPLE

Pages

PUBLICATIONS AND COMMUNICATIONS

2011

Helft, L., et al. LRR conservation mapping to predict functional sites within protein leucine-rich repeat domains. PloS one 6, e21614 (2011).
Solernou, A. & Fernández-Recio, J. pyDockCG: new coarse-grained potential for protein-protein docking. The journal of physical chemistry. B 115, 6032-9 (2011).
Raimondi, F., Portella, G., Orozco, M. & Fanelli, F. Nucleotide binding switches the information flow in ras GTPases. PLoS computational biology 7, e1001098 (2011).
Orozco, M., et al. Coarse Grained Representation of Protein Flexibility. Foundations, successes and shortcomings. (2011).
Fernández-Recio, J. Prediction of protein binding sites and hot spots. WIREs Comput. Mol. Sci. 1, 680-698 (2011).
Fleishman, S.J., et al. Community-wide assessment of protein-interface modeling suggests improvements to design methodology. Journal of molecular biology 414, 289-302 (2011).