Molecular modelling and bioinformatics

Modesto Orozco

Principal Investigator
Professor (Biochemistry and Molecular Biology Dept. - UB)

Office Tel : +34 93 403 71 56
Lab Tel : +34 93 403 71 55
e-mail : modesto.orozcoirbbarcelona.org

Research Interests

Our research focuses on the study of molecular recognition processes of biological significance from methodological and application points of view. The main subjects addressed are the structure of non-standard nucleic acids, the dynamic properties of macromolecules, and protein-ligand and protein-protein recognition.

Research Lines

Methodological aspects

• Analysis of the effect of solvent in molecular recognition. Continuum methods are compared to analyse explicit solvent simulations.
• Fine-tuning of the parametrization of molecular dynamics simulations.

Studies on Small Models

• Theoretical studies of small model systems of large biological impact. This includes, among others, tautomeric and isomerism processes, stacking interactions, salt bridges, hydrogen bonding, cation-π interactions, and general mechanisms of molecular recognition.

Studies on Proteins

• We study the basis of protein interactions, including those of pharmacological importance. In addition, we develop methods to examine both protein-protein and protein-ligand recognition.
• We analyse protein flexibility using massive molecular dynamics simulations.

Studies on Nucleic Acids

• We use molecular dynamics and statistical mechanics to examine 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.

Bioinformatics

• Data mining of genomic DNA to identify regions with unusual structures or unusual mechanical properties.
• Development of algorithms for the prediction of the pathological character of single nucleotide polymorphisms.
• Structural study of alternative splicing in proteins.

Funding

This group receives financial support from the following sources:

• Fundación Ramón Areces (Ramón Areces Foundation)
  
• Ministerio de Educación y Ciencia (MEC - Spanish Ministry of Science and Education)
• Fundación BBVA (BBVA Foundation)
  
• CIRIT – Generalitat de Catalunya (Interdepartmental Committee for Technological Research and Innovation)(Government of Catalonia)
  

More info

• Orozco Group Scientific Report 2007
• Orozco Group Scientific Report 2005-2006
• Molecular Modelling Website

Molecular modelling and bioinformatics

COCO: A simple tool to enrich the representation of conformational variability in NMR structures
Laughton CA, Orozco M and Vranken W
Proteins ([Epub ahead of print]) (2008)

Exploring the suitability of coarse-grained techniques for the representation of protein dynamics
Emperador A, Carrillo O, Rueda M and Orozco M
Biophys J, 95 (5), 2127-2138 (2008)

Interoperability with Moby 1.0--it's better than sharing your toothbrush!
The Biomoby consortium (including Orozco M, Gelpí JL and others)
Brief Bioinform, 9 (3), 220-231 (2008)

Extension of the MST continuum solvation model to the RM1 semiempirical Hamiltonian
Forti F, Barril X, Luque FJ and Orozco M
J Comput Chem, 29 (4), 578-587 (2008)

Theoretical analysis of antisense duplexes: determinants of the RNase H susceptibility
Noy A, Luque FJ and Orozco M
J Am Chem Soc, 130 (11), 3486-3496 (2008)

8-Amino guanine accelerates tetramolecular G-quadruplex formation
Gros J, Aviñó A, Lopez de la Osa J, González C, Lacroix L, Pérez A, Orozco M, Eritja R and Mergny JL
Chem Commun, 7 (25), 2926-2928 (2008)

GRID-MD-A tool for massive simulation of protein channels
Carrillo O and Orozco M
Proteins, 70 (3), 892-899 (2008)

Ab initio study of naphtho-homologated DNA bases
Vázquez-Mayogoita A, Huertas O, Fuentes-Cabrera M, Sumpter BG, Orozco M and Luque FJ
J Phys Chem B, 112 (7), 2179-2186 (2008)

Recent advances in the study of nucleic acid flexibility by molecular dynamics
Orozco M, Noy A and Pérez A
Curr Opin Struct Biol, 18 (2), 185-193 (2008)

Derivation of distributed models of atomic polarizability for molecular simulations
Soteras I, Curutchet C, Bidon-Chanal A, Dehez F, Angyan J, Orozco M, Chipot C and Luque FJ
J Chem Theory Comput, 3 (6), 1901-1913 (2007)

The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane
Fort J, de la Ballina LR, Burghardt HE, Ferrer-Costa C, Turnay J, Ferrer-Orta C, Usón I, Zorzano A, Fernández-Recio J, Orozco M, Lizarbe MA, Fita I and Palacín M
J Biol Chem, 282 (43), 31444-31452 (2007)

Binding affinities of oligonucleotides and PNAs containing phenoxazine and G-clamp cytosine analogues are unusually sequence-dependent
Ortega JA, Blas JR, Orozco M, Grandas A, Pedroso E and Robles J
Org Lett, 9 (22), 4503-4506 (2007)

Dynamics of B-DNA on the microsecond time scale
Pérez A, Luque FJ and Orozco M
J Am Chem Soc, 129 (47), 14739-14745 (2007)

Theoretical study of large conformational transitions in DNA: the B<-->A conformational change in water and ethanol/water
Noy A, Pérez A, Laughton CA and Orozco M
Nucleic Acids Res, 35 (10), 3330-3338 (2007)

Thorough validation of protein normal mode analysis: a comparative study with essential dynamics
Rueda M, Chacón P and Orozco M
Structure, 15 (5), 565-575 (2007)

The (in)dependence of alternative splicing and gene duplication
Talavera D, Vogel C, Orozco M, Teichmann SA and de la Cruz X
PLoS Comput Biol, 3 (3), 375-388 (2007)

Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers
Pérez A, Marchán I, Svozil D, Sponer J, Cheatham TE 3rd, Laughton CA and Orozco M
Biophys J, 92 (11), 3817-3829 (2007)

A procedure for identifying homologous alternative splicing events
Talavera D, Hospital A, Orozco M and de la Cruz X
BMC Bioinformatics, 8, 260-271 (2007)

A consensus view of protein dynamics
Rueda M, Ferrer-Costa C, Meyer T, Pérez A, Camps J, Hospital A, Gelpí JL and Orozco M
Proc Natl Acad Sci USA, 104 (3), 796-801 (2007)

Exploring the dynamics of calix[4]pyrrole: effect of solvent and fluorine substitution
Blas JR, López-Bes JM, Márquez M, Sessler JL, Luque FJ and Orozco M
Chemistry, 13 (4), 1108-1116 (2007)

Characterization of compensated mutations in terms of structural and physico-chemical properties
Ferrer-Costa C, Orozco M and de la Cruz X
J Mol Biol, 365 (1), 249-256 (2007)

Dissection of the recognition properties of p38 MAP kinase. Determination of the binding mode of a new pyridinyl-heterocycle inhibitor family
Soliva R, Gelpi JL, Almansa C, Virgili M and Orozco M
J Med Chem, 50 (2), 283-293 (2007)

A hydrophobic similarity analysis of solvation effects on nucleic acid bases
Muñoz-Muriedas J, Barril X, López JM, Orozco M and Luque FJ
J Mol Model, 13 (2), 357-365 (2007)

Triplex formation using oligonucleotide clamps carrying 8-aminopurines
Aviñó A, Grimau MG, Alvira M, Eritja R, Gargallo R, Orozco M and González C
Nucleosides Nucleotides Nucleic Acids, 26 (8-9), 979-983 (2007)

Continuum analysis of conformational sampling in solution. In Continuum Solvation Models in Chemical Physics: Theory and Application
Orozco M, Marchán I and Soteras I
Mennucci B and Cammi R (Eds), Elsevier, 499-522 (2007)

Determining promoter location based on DNA structure first-principles calculations
Goñi JR, Pérez A, Torrents D and Orozco M
Genome Biol, 8 (12), R263 (2007)

A fast method for the determination of fractional contributions to solvation in proteins
Talavera D, Morreale A, Meyer T, Hospital A, Ferrer-Costa C, Gelpi JL, de la Cruz X, Soliva R, Luque FJ and Orozco M
Protein Sci, 15 (11), 2525-2533 (2006)

Local aromaticity in natural nucleobases and their size-expanded benzo-fused derivatives
Huertas O, Poater J, Fuentes-Cabrera M, Orozco M, Solà M and Luque FJ
J Phys Chem A, 110 (44), 12249-12258 (2006)

Dispersion and repulsion contributions to the solvation free energy: comparison of quantum mechanical and classical approaches in the polarizable continuum model
Curutchet C, Orozco M, Luque FJ, Mennucci B and Tomasi J
J Comput Chem, 27 (15), 1769-1780 (2006)

On the origin of the stereoselectivity in the alkylation of oxazolopiperidone enolates
Soteras I, Lozano O, Gómez-Esqué A, Escolano C, Orozco M, Amat M, Bosch J and Luque FJ
J Am Chem Soc, 128 (20), 6581-6588 (2006)

G-quadruplexes can maintain their structure in the gas phase
Rueda M, Luque FJ and Orozco M
J Am Chem Soc, 128 (11), 3608-3619 (2006)

Exploring the reasons for the large density of triplex-forming oligonucleotide target sequences in the human regulatory regions
Goñi JR, Vaquerizas JM, Dopazo J and Orozco M
BMC Genomics, 7, 63-72 (2006)

Nature of base stacking: reference quantum-chemical stacking energies in ten unique B-DNA base-pair steps
Sponer J, Jurecka P, Marchan I, Luque FJ, Orozco M and Hobza P
Chemistry, 12 (10), 2854-2865 (2006)

Destabilization of quadruplex DNA by 8-aminoguanine
López de la Osa J, González C, Gargallo R, Rueda M, Cubero E, Orozco M, Aviñó A and Eritja R
Chembiochem, 7 (1), 46-48 (2006)

Benzoderivatives of nucleic acid bases as modified DNA building blocks
Huertas O, Blas JR, Soteras I, Orozco M and Luque FJ
J Phys Chem A, 110 (2), 510-518 (2006)

Theoretical study of the Hoogsteen-Watson-Crick junctions in DNA
Cubero E, Luque FJ and Orozco M
Biophys J, 90 (3), 1000-1008 (2006)

Data mining of molecular dynamics trajectories of nucleic acids
Noy A, Meyer T, Rueda M, Ferrer C, Valencia A, Pérez A, de la Cruz X, López-Bes JM, Pouplana R, Fernandez-Recio J, Luque FJ and Orozco M
J Biomol Struct Dyn, 23 (4), 447-456 (2006)

Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
Bidon-Chanal A, Martí MA, Crespo A, Milani M, Orozco M, Bolognesi M, Luque FJ and Estrin DA
Proteins, 64 (2), 457-464 (2006)

Essential dynamics: a tool for efficient trajectory compression and management
Meyer T, Ferrer-Costa C, Pérez A, Rueda M, Bidon-Chanal A, Luque FJ, Laughton CA and Orozco M
J Chem Theory Comput, 2 (2), 251-258 (2006)

Aromaticity-induced changes in electronic properties of size-expanded DNA bases: Case of xC
Fuentes-Cabrera M, Lipkowski P, Huertas O, Sumpter BG, Orozco M, Luque FJ, Wells JC and Leszczynski J
Int J Quantum Chem, 106 (11), 2339-2346 (2006)

Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer's disease
Muñoz-Ruiz P, Rubio L, García-Palomero E, Dorronsoro I, del Monte-Millán M, Valenzuela R, Usán P, de Austria C, Bartolini M, Andrisano V, Bidon-Chanal A, Orozco M, Luque FJ, Medina M and Martínez A
J Med Chem, 48 (23), 7223-7233 (2005)

MST continuum study of the hydration free energies of monovalent ionic species
Curutchet C, Bidon-Chanal A, Soteras I, Orozco M and Luque FJ
J Phys Chem B, 109 (8), 3565-3574 (2005)

Theoretical study of the truncated hemoglobin HbN: exploring the molecular basis of the NO detoxification mechanism
Crespo A, Martí MA, Kalko SG, Morreale A, Orozco M, Gelpi JL, Luque FJ and Estrin DA
J Am Chem Soc, 127 (12), 4433-4444 (2005)

Hydrophobic molecular similarity from MST fractional contributions to the octanol/water partition coefficient
Muñoz-Muriedas J, Perspicace S, Bech N, Guccione S, Orozco M and Luque FJ
J Comput Aided Mol Des, 19 (6), 401-419 (2005)

PMUT: a web-based tool for the annotation of pathological mutations on proteins
Ferrer-Costa C, Gelpí JL, Zamakola L, Parraga I, de la Cruz X and Orozco M
Bioinformatics, 21 (14), 3176-3178 (2005)

PupasView: a visual tool for selecting suitable SNPs, with putative pathological effect in genes, for genotyping purposes
Conde L, Vaquerizas JM, Ferrer-Costa C, de la Cruz X, Orozco M and Dopazo J
Nucleic Acids Res, 3, 501-505 (2005)

Partition of protein solvation into group contributions from molecular dynamics simulations
Morreale A, de la Cruz X, Meyer T, Gelpí JL, Luque FJ and Orozco M
Proteins, 58 (1), 101-109 (2005)

Use of bioinformatics tools for the annotation of disease-associated mutations in animal models
Ferrer-Costa C, Orozco M and de la Cruz X
Proteins, 61 (4), 878-887 (2005)

Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE
Alonso D, Dorronsoro I, Rubio L, Muñoz P, García-Palomero E, Del Monte M, Bidon-Chanal A, Orozco M, Luque FJ, Castro A, Medina M and Martínez A
Bioorg Med Chem, 13 (24), 6588-6597 (2005)

Nature of minor-groove binders-DNA complexes in the gas phase
Rueda M, Luque FJ and Orozco M
J Am Chem Soc, 127 (33), 11690-11698 (2005)

Are the hydrogen bonds of RNA (AU) stronger than those of DNA (AT)? A quantum mechanics study
Pérez A, Sponer J, Jurecka P, Hobza P, Luque FJ and Orozco M
Chemistry, 11 (17), 5062-5066 (2005)

Extension of the MST model to the IEF formalism: HF and B3LYP parametrizations
Soteras I, Curutchet C, Bidon-Chanal A, Orozco M and Luque FJ
J Mol Struct Theochem, 727 (1-3), 29-40 (2005)

Structure, recognition properties, and flexibility of the DNA.RNA hybrid
Noy A, Pérez A, Márquez M, Luque FJ and Orozco M
J Am Chem Soc, 127 (13), 4910-4920 (2005)

Exploring the essential dynamics of B-DNA
Pérez A, Blas JR, Rueda M, López-Bes JM, de la Cruz X and Orozco M
J Chem Theory Comput, 1, 790-800 (2005)

Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity
Marti L, Abella A, De La Cruz X, García-Vicente S, Unzeta M, Carpéné C, Palacín M, Testar X, Orozco M and Zorzano A
J Med Chem, 47 (20), 4865-4874 (2004)

Relative flexibility of DNA and RNA: a molecular dynamics study
Noy A, Pérez A, Lankas F, Javier Luque F and Orozco M
J Mol Biol, 343 (3), 627-638 (2004)

Unconventional interactions between water and heterocyclic nitrogens in protein structures
Stollar EJ, Gelpí JL, Velankar S, Golovin A, Orozco M and Luisi BF
Proteins, 57 (1), 1-8 (2004)

The relative flexibility of B-DNA and A-RNA duplexes: database analysis
Pérez A, Noy A, Lankas F, Luque FJ and Orozco M
Nucleic Acids Res, 32 (20), 6144-6151 (2004)

Theoretical study of the guanine --> 6-thioguanine substitution in duplexes, triplexes, and tetraplexes
Spacková N, Cubero E, Sponer J and Orozco M
J Am Chem Soc, 126 (44), 14642-14650 (2004)

Linear response theory: an alternative to PB and GB methods for the analysis of molecular dynamics trajectories?
Morreale A, de la Cruz X, Meyer T, Gelpí JL, Luque FJ and Orozco M
Proteins, 57 (3), 458-467 (2004)

Effect of bulky lesions on DNA: Solution structure of a DNA duplex containing a cholesterol adduct
Gómez-Pinto I, Cubero E, Kalko SG, Monaco V, van der Marel G, van Boom JH, Orozco M and González C
J Biol Chem, 279 (23), 24552-24560 (2004)

Functional and structural conservation of CBS domains from CLC chloride channels
Estévez R, Pusch M, Ferrer-Costa C, Orozco M and Jentsch TJ
J Physiol, 557 (Pt2), 363-378 (2004)

Alternative splicing mechanisms for the modulation of protein function: conservation between human and other species
Valenzuela A, Talavera D, Orozco M and de la Cruz X
J Mol Biol, 335 (2), 495-502 (2004)

Triplex-forming oligonucleotide target sequences in the human genome
Goñi JR, de la Cruz X and Orozco M
Nucleic Acids Res, 32 (1), 354-360 (2004)

Unique tautomeric properties of isoguanine
Blas JR, Luque FJ and Orozco M
J Am Chem Soc, 126 (1), 154-164 (2004)

Sequence-based prediction of pathological mutations
Ferrer-Costa C, Orozco M and de la Cruz X
Proteins, 57 (4), 811-819 (2004)

Exploring the counterion atmosphere around DNA: what can be learned from molecular dynamics simulations?
Rueda M, Cubero E, Laughton CA and Orozco M
Biophys J, 87 (2), 800-811 (2004)

Antiparallel triple helices. Structural characteristics and stabilization by 8-amino derivatives
Aviñó A, Cubero E, González C, Eritja R and Orozco M
J Am Chem Soc, 125 (51), 13127-16138 (2003)

Molecular modelling and bioinformatics

Modesto Orozco

Principal Investigator
Professor (Biochemistry and Molecular Biology Dept. - UB)

Office Tel : +34 93 403 71 56
Lab Tel : +34 93 403 71 55
e-mail : modesto.orozcoirbbarcelona.org

Research Associate
Xavier de la Cruz Montserrat (ICREA Research Professor)
tel +34 93 403 71 58
xavier.delacruzirbbarcelona.org

Juan Fernandez Recio
tel +34 93 403 71 58
juan.fernandez.recioirbbarcelona.org

Josep Lluís Gelpí
tel +34 93 403 47 07
josep.gelpiirbbarcelona.org

Agustí Emperador
tel +34 93 403 71 55
agusti.emperadorirbbarcelona.org

Postdoctoral Fellow
Oliver Carrillo
tel +34 93 403 71 55
oliver.carrilloirbbarcelona.org

Marco D'Abramo
tel +34 93 403 71 55
marco.dabramoirbbarcelona.org

Rebeca García Fandiño
tel +34 93 403 71 55
rebeca.garciairbbarcelona.org

Guillem Portella Carbó
tel +34 93 403 71 55
guillem.portellairbbarcelona.org

PhD Student
Adam Hospital
tel +34 93 403 71 55
adam.hospitalirbbarcelona.org

Sergio Lois
tel +34 93 403 71 55
sergio.loisirbbarcelona.org

Tim Meyer
tel +34 93 403 71 55
tim.meyerirbbarcelona.org

Agnes Noy
tel +34 93 403 71 55
agnes.noyirbbarcelona.org

Alberto Pérez
tel +34 93 403 71 55
alberto.perezirbbarcelona.org

David Piedra
tel +34 93 403 71 55
david.piedrairbbarcelona.org

Annalisa Arcella
tel +34 93 403 71 55
annalisa.arcellairbbarcelona.org

Ignacio Faustino Plo
tel +34 93 403 71 55
ignacio.faustinoirbbarcelona.org

Jordi Morata Chirivella
tel +34 93 403 71 55
jordi.moratairbbarcelona.org

Laura Orellana
tel +34 93 403 71 55
laura.orellanairbbarcelona.org

Mireia Ruiz
tel +34 93 403 71 55
mireia.ruizirbbarcelona.org

Ozgen Deniz
tel +34 93 403 71 55
ozgen.denizirbbarcelona.org

Research Assistant
Iván Párraga
tel +34 93 403 71 55
ivan.parragairbbarcelona.org

José Antonio Alcántara
tel +34 93 403 71 55
jose.alcantarairbbarcelona.org

Administrative Assistant
Margarita Pedro
tel +34 93 403 71 55
margarita.pedroirbbarcelona.org

Lab Technician
Damjan Cicin Sain
+34 93 403 7155
damjan.cicinirbbarcelona.org

Molecular modelling and bioinformatics

• 1 April 2008
  Revista UB
  Un nou codi en el genoma
  
• 29 January 2008
  El Punt (Girona)
  Científics de Barcelona troben un codi nou en el genoma
  
• 28 January 2008
  Europa Press
  Científicos españoles revelan la existencia de un código en el genoma, clave en la regulación de la expresión génica
  
• 28 January 2008
  Hispanidad
  Científicos españoles revelan la existencia de un código en el genoma, clave en la regulación de la expresión génica
  
• 28 January 2008
  Terra
  Científicos barceloneses descubren un nuevo código en el genoma
  
• 29 January 2008
  Diario Médico
  Hallan un código en el genoma desconocido hasta el momento
  
• 29 January 2008
  El Punt (Barcelona)
  Científics de Barcelona troben un codi desconegut en el genoma
  
• 29 January 2008
  Diari de Girona
  Científics barcelonins descobreixen un nou codi en el genoma
  
• 29 January 2008
  Hoy Extremadura
  Descubren un nuevo código en el genoma
  
• 28 January 2008
  Science News
  A group of researchers discover a new code in the genome
  

  The finding of researchers at the Barcelona Supercomputing Center (BSC) and the Institute for Research in Biomedicine (IRB Barcelona) has been possible thanks to the calculation capacity of the MareNostrum supercomputer

• 2 July 2007
  El Periódico de Catalunya
  El 'Mare Nostrum' simularà el funcionament dels òrgans
  
• 3 March 2007
  Prensa.com
  Superordenador completa el mayor catálogo de proteí­nas del mundo
  
• 15 January 2007
  La opinión de Tenerife
  Cientí­ficos diseñan el mapa de proteí­nas con el ordenador 'Marenostrum'
  
• 11 January 2007
  Medical News Today
  Dynamic map of proteins revealed by Spanish scientists
  
• 10 January 2007
  Cordis
  Cientí­ficos españoles revelan un mapa dinámico de proteí­nas
  
• 10 January 2007
  Science Daily
  Spanish scientists reveal dynamic map of proteins, possibilities for new drugs
  
• 10 January 2007
  Heraldo de Aragón
  Crean un mapa que refleja todos los movimientos de las proteí­nas
  

  The research carried out by Prof. Modesto Orozco in the paper Heraldo de Aragón.

• 10 January 2007
  Diario Médico
  Un grupo español realiza un atlas del comportamiento dinámico de las proteí­nas
  

  The research carried out by Prof. Modesto Orozco in the Spanish paper Diario Médico

• 10 January 2007
  El Paí­s
  Cientí­ficos españoles crean un programa que predice la estructura de las proteí­nas
  

  The research leaded by Prof. Modesto Orozco in the Spanish newspaper El Pais

• 10 January 2007
  ABC
  Marenostrum muestra el primer mapa dinámico de las proteí­nas
  

  The research leaded by Prof. Modesto Orozco in the Spanish newspaper ABC

• 9 January 2007
  La Voz de Galicia
  El superordenador permite dibujar un "mapa" con los movimientos de las proteínas
  

  Prof. Modesto Orozco research on the Galician newspaper La Voz de Galicia

• 9 January 2007
  Science News
  Spanish scientists reveal dynamic map of proteins
  

  This work provides important basic information on the flexibility of proteins and their ability to link with other molecules, an area of study which opens enormous possibilities for the design of new drugs. The study appears in this week’s online version of the prestigious scientific journal, Proceedings of the National Academy of Sciences USA.

• 9 January 2007
  Feature Article
  Proteins and supercomputers: using computation to unravel the rules that govern life
  

  Biocomputation, with supercomputers as key tools, is allowing scientists to respond to many unanswered questions about these crucial agents for life.

• 4 December 2005
  El Paí­s
  Proteínas al por mayor
  

  Biochemist Modesto Orozco is developing a large library that will contain 1,900 proteins in movement