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Rafael Juárez,
María Moreno Oliva,
Mar Ramos,
José L Segura,
Carlos Alemán,
Francisco Rodríguez-Ropero, David Curcó,
Francisco Montilla,
Veaceslav Coropceanu,
Jean Luc Brédas,
Yabing Qi,
Antoine Kahn,
M Carmen Ruiz Delgado,
Juan Casado,
Juan T López Navarrete
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ABSTRACT: A new hexaazatriphenylene (HAT) derivative formed by the fusion of three HAT units has been prepared and its electronic and molecular structures have been fully characterized by optical and vibrational Raman spectroscopy, electrochemistry, solid-state UV and inverse photoemission spectroscopy (UPS and IPES), and by quantum-chemical calculations. A comparative HAT versus tri-HAT study was performed. The fusion of three HAT molecules causes modifications in the optical and electrochemical properties consistent with enhanced π-electron delocalization attained in a bigger planar core. Such combined experimental and theoretical studies are useful to balance chemical design with supramolecular engineering directed to find enhanced characteristics for new organic semiconductor applications.
Chemistry 08/2011; 17(37):10312-22. · 5.93 Impact Factor
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ABSTRACT: Recently, we reported a database (Noncoded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of nonproteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally established conformational propensities, and applications (Revilla-López et al., J Phys Chem B 2010;114:7413-7422). The database initially contained the information available for α-tetrasubstituted α-amino acids. In this work, we extend NCAD to three families of compounds, which can be used to engineer peptides and proteins incorporating modifications at the--NHCO--peptide bond. Such families are: N-substituted α-amino acids, thio-α-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 3(10)-helix with respect to the α-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database.
Proteins Structure Function and Bioinformatics 06/2011; 79(6):1841-52. · 3.39 Impact Factor
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ABSTRACT: A computational strategy to model flexible molecules tethered to a rigid inert surface is presented. The strategy is able to provide uncorrelated relaxed microstructures at the atomistic level. It combines an algorithm to generate molecules tethered to the surface without atomic overlaps, a method to insert solvent molecules and ions in the simulation box, and a powerful relaxation procedure. The reliability of the strategy has been investigated by simulating two different systems: (i) mixed monolayers consisting of binary mixtures of long-chain alkyl thiols of different lengths adsorbed on a rigid inert surface and (ii) CREKA (Cys-Arg-Glu-Lys-Ala), a short linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, covalently tethered to a rigid inert surface in aqueous solution. In the first, we examined the segregation of the two species in the monolayers using different long-chain:short-chain ratios, whereas in the second, we explored the conformational space of CREKA and ions distribution considering densities of peptides per nm(2) ranging from 0.03 to 1.67. Results indicate a spontaneous segregation in alkyl thiol monolayers, which enhances when the concentration of longest chains increases. However, the whole conformational profile of CREKA depends on the number of molecules tethered to the surface pointing out the large influence of molecular density on the intermolecular interactions, even though the bioactive conformation was found as the most stable in all cases.
Journal of Computational Chemistry 03/2011; 32(4):607-19. · 4.58 Impact Factor
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ABSTRACT: This work presents a computational strategy to model flexible molecules tethered to a metallic rigid surface. The method is based on a previously developed procedure for inert surfaces, in which peptide-surface interactions were not considered. This procedure is able to generate uncorrelated relaxed microstructures at the atomistic level of systems containing relatively high densities of peptides tethered to the surface. The reliability of the strategy has been tested by simulating CREKA (Cys-Arg-Glu-Lys-Ala), a short linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, covalently tethered to a gold surface, results being compared with those obtained when the surface was represented as inert. The results indicate that the whole conformational profile of CREKA presents some correlation with the chemical activity of the surface, even though the bioactive conformation was found as the most favored in all cases. Specifically, simulations reflect that consideration of the peptide-surface interactions affect the geometrical orientation of the side chains, whereas the main chain conformation does not undergo significant modifications.
Journal of Peptide Science 02/2011; 17(2):132-8. · 1.80 Impact Factor
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ABSTRACT: Atomistic simulations have been carried to investigate electric field induced transport of hydronium ions in a sulfonated poly(styrene-co-divinylbenzene) membrane. In order to provide a good description of this cross-linked material, a methodology has been explicitly designed to construct a reliable model of the hydrated membrane. This model has been used to carry out molecular dynamics simulations in presence of electric fields, which varied from 0.001 to 3.0 V3 nm-1. Results show that the electric field affects the structure of the membrane producing both a redistribution of the unoccupied volume, which modifies the heterogeneity of the resin, and a rearrangement of the negatively charged sulfonate groups, which undergo a systematic alignment along the electric field direction. As was expected, the mobility of hydronium ions is enhanced with the strength of the electric field. Moreover, the electric field induces a significant rearrangement of the sulfonate groups, which is evidenced by the alignment of theC-S bonds along the direction of the field. The membrane has been found to behave as a spring, in which the force exerted by the electric field acts in opposite sense to the force exerted by the internal structure of the cross-linked material. Postprint (published version)
Macromolecules 12/2010; 43(24):10521-10527. · 5.17 Impact Factor
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ABSTRACT: Amorphous polyaniline emeraldine base has been investigated using atomistic classical molecular dynamics simulations. Initially, different sets of force-field parameters, which differ in the atomic charges and/or the van der Waals parameters, were tested. The experimental density of polyaniline was satisfactorily reproduced using the following combination: (i) equilibrium bond lengths, equilibrium bond angles, and electrostatic charges derived from quantum mechanical calculations and (ii) van der Waals parameters extrapolated from GROMOS for all atoms with the exception of the CH pseudoparticles of the phenyl ring, which were taken from an anisotropic united atom potential. Next, this force field was used to investigate the structure of the polymer in the amorphous state, the trajectories performed for this purpose allowing accumulation of 750 ns. Analyses of the energies evidence that the interactions between one repeating unit containing an amine nitrogen atom and another unit with an imine nitrogen are favored with respect to those between two identical repeating units. This conclusion is also supported by quantum mechanical and quantum mechanical/molecular mechanics calculations. On the other hand, the partial radial distribution functions indicate that this material only exhibits short-range intramolecular correlation, which is in excellent agreement with experimental evidence.
The Journal of Physical Chemistry B 08/2010; 114(30):9771-7. · 3.70 Impact Factor
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Guillem Revilla-López,
Juan Torras, David Curcó,
Jordi Casanovas,
M Isabel Calaza,
David Zanuy,
Ana I Jiménez,
Carlos Cativiela,
Ruth Nussinov,
Piotr Grodzinski,
Carlos Alemán
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ABSTRACT: Peptides and proteins find an ever-increasing number of applications in the biomedical and materials engineering fields. The use of non-proteinogenic amino acids endowed with diverse physicochemical and structural features opens the possibility to design proteins and peptides with novel properties and functions. Moreover, non-proteinogenic residues are particularly useful to control the three-dimensional arrangement of peptidic chains, which is a crucial issue for most applications. However, information regarding such amino acids--also called non-coded, non-canonical, or non-standard--is usually scattered among publications specialized in quite diverse fields as well as in patents. Making all these data useful to the scientific community requires new tools and a framework for their assembly and coherent organization. We have successfully compiled, organized, and built a database (NCAD, Non-Coded Amino acids Database) containing information about the intrinsic conformational preferences of non-proteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, conformational propensities established experimentally, and applications. The architecture of the database is presented in this work together with the first family of non-coded residues included, namely, alpha-tetrasubstituted alpha-amino acids. Furthermore, the NCAD usefulness is demonstrated through a test-case application example.
The Journal of Physical Chemistry B 06/2010; 114(21):7413-22. · 3.70 Impact Factor
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Journal of Chemical Information and Modeling 07/2009; 49(7):1623-9. · 4.68 Impact Factor
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ABSTRACT: The conformational properties of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence labeled with fluorescein, a fluorescent dye attached to the Cys through a flexible linker have been examined using molecular dynamics simulations. The CREKA sequence has been identified as a tumor-homing peptide that effectively binds to clotted plasma proteins. Before conformational exploration, the molecular geometry, basicity and spectroscopic properties of this dye, which is essential for the imaging the peptide activity, have been examined using quantum mechanical calculations, with the results also allowing determination of the force-field parameters required for classical simulations. Minimum energy conformations derived from the conformational search have been classified using clustering analyses with criteria based on both the existence of interactions and backbone geometric similarity. The results have been compared with those reported for isolated CREKA (peptide without dye). We found that the fluorescein affects the energy distribution of the minimum energy conformations, with the repulsive steric interactions induced by the dye producing shifting the distribution towards higher energy values. Interestingly, although the structural characteristics of the bioactive conformation identified for CREKA are not perturbed by the dye, it is less stable when the peptide is attached to the dye than in other chemical environments previously studied (isolated peptide, peptide attached to the surface of a protein, and peptide inserted in a phage display protein).
Biopolymers 01/2009; 92(2):83-93. · 2.87 Impact Factor
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ABSTRACT: Recently, a potentially powerful strategy based on phage-display libraries has been presented to target tumors via homing peptides attached to nanoparticles. The Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence has been identified as a tumor-homing peptide that binds to clotted plasmas proteins present in tumor vessels and interstitium. The aim of this work consists of mapping the conformational profile of CREKA to identify the bioactive conformation. For this purpose, a conformational search procedure based on modified simulated annealing combined with molecular dynamics was applied to three systems that mimic the experimentally used conditions: (i) the free peptide; (ii) the peptide attached to a nanoparticle; and (iii) the peptide inserted in a phage display protein. In addition, the free peptide was simulated in an ionized aqueous solution environment, which mimics the ionic strength of the physiological medium. Accessible minima of all simulated systems reveal a multiple interaction pattern involving the ionized side chains of Arg, Glu, and Lys, which induces a beta-turn motif in the backbone observed in all simulated CREKA systems.
The Journal of Physical Chemistry B 08/2008; 112(29):8692-700. · 3.70 Impact Factor
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ABSTRACT: Nanotubular structures constructed using self-assembled beta-helical protein building blocks one atop the other have been coarsened to develop a mesoscopic potential that reproduces the intermolecular interaction energies provided by atomistic force-fields. The resulting potential consists of an analytical expression that depends exclusively on the distance and the relative orientation between the two interacting entities. In spite of its complexity, this coarse-grained potential reproduces satisfactorily the energetic properties of two interacting building blocks. The coarse-grained potential has been used to predict that the interaction between building blocks formed by residues 131-165 of E. coli galactoside acteyltransferase becomes repulsive when the size of the nanotube is larger than a threshold, that is, about 45 self-assembled building blocks.
The Journal of Physical Chemistry B 01/2008; 111(50):14006-11. · 3.70 Impact Factor
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ABSTRACT: We present a coarse-graining procedure to construct models of amorphous polymers. The method, which was applied to polyethylene, is based on a generation-relaxation strategy previously developed to provide independent atomistic microstructures. The coarse-graining was performed by assigning positions to mesoscopic particles denoted blobs, which represent groups of atoms, through distance, angle and dihedral distribution functions. The interaction energy between pairs of blobs was evaluated through a soft potential, whose parameters were derived from atomistic models. Three levels of coarse-graining that differ in the number of atoms included in the blob have been considered. The structural and energy-related properties calculated using the coarse-grained models developed in this study are in good agreement with those obtained using atomistic simulations.
Journal of Computational Chemistry 10/2007; 28(12):1929-35. · 4.58 Impact Factor
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ABSTRACT: A general strategy to develop coarse-grained models of beta-helical protein fragments is presented. The procedure has been applied to a building block formed by a two-turn repeat motif from E. coli galactoside acetyltransferase, which is able to provide a very stable self-assembled tubular nanoconstruct upon stacking of its replicas. For this purpose, first, we have developed a computational scheme to sample very efficiently the configurational space of the building block. This method, which is inspired by a strategy recently designed to study amorphous polymers and by an advanced Monte Carlo algorithm, provides a large ensemble of uncorrelated configurations at a very reasonable computational cost. The atomistic configurations provided by this method have been used to obtain a coarse-grained model that describes the amino acids with fewer particles than those required for full atomistic detail, i.e., two, three, or four depending on the chemical nature of the amino acid. Coarse-grained potentials have been developed considering the following types of interactions: (i) electrostatic and van der Waals interactions between residues i and i + n with n >/= 2; (ii) interactions between residues i and i + 1; and (c) intra-residue interactions. The reliability of the proposed model has been tested by comparing the atomistic and coarse-grained energies calculated for a large number of independent configurations of the beta-helical building block.
The Journal of Physical Chemistry B 09/2007; 111(35):10538-49. · 3.70 Impact Factor
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ABSTRACT: A very efficient computational procedure, which was previously developed to generate and relax atomistic models of linear and comb-like amorphous polymers, has been adapted to model the amorphous phase of polycyclic systems. The strategy, which is a based in a generation algorithm that eliminates the torsion strain and a simple Monte Carlo Metropolis method to relax the generated structures, has been used to predict the density of amorphous polythiophene by combining NVT and NPT simulations. The theoretical value is in the excellent agreement with the experimental one, the former being overestimated by only 3-5%. Next, the molecular conformation and the packing of the rings were studied in detail. Interestingly, the amorphous phase of polythiophene can be described as a packing of elongated molecular chains more or less aligned in the same direction, in which the thiophene rings close in the space but belonging to different chains tend to adopt approximate parallel or antiparallel displaced pi-stacked arrangements.
Journal of Computational Chemistry 08/2007; 28(10):1743-9. · 4.58 Impact Factor
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ABSTRACT: Torsional and the electrostatic parameters for molecular mechanics studies of retro-inverso modified peptides have been developed using quantum mechanical calculations. The resulting parameters have been compared with those calculated for conventional peptides. Rotational profiles, which were obtained spanning the corresponding dihedral angle, were corrected by removing the energy contributions associated to changes in interactions different from torsion under study. For this purpose, the torsional energy associated to each point of the profiles was estimated as the corresponding quantum mechanical energy minus the bonding and nonbonding energy contributions produced by the perturbations that the variation of the spanned dihedral angle causes in the bond distances, bond angles and the other dihedral angles. These energies were calculated using force-field expressions. The corrected profiles were fitted to a three-term Fourier expansion to derive the torsional parameters. Atomic charges for retro-inverso modified residues were derived from the rigorously calculated quantum mechanical electrostatic potential. Furthermore, the reliability of electrostatic models based on geometry-dependent charges and fixed charges has been examined.
Journal of Computer-Aided Molecular Design 02/2006; 20(1):13-25. · 3.39 Impact Factor
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ABSTRACT: Both the intermolecular interaction energies and the geometries for M... thiophene, M... pyrrole, M(n+)... thiophene, and M(n+)... pyrrole (with M = Li , Na, K, Ca, and Mg; and M(n+) = Li+, Na+, K+, Ca2+, and Mg2+) have been estimated using four commonly used density functional theory (DFT) methods: B3LYP, B3PW91, PBE, and MPW1PW91. Results have been compared to those provided by HF, MP2, and MP4 conventional ab initio methods. The PBE and MPW1PW91 are the only DFT methods able to provide a reasonable description of the M...pi complexes. Regarding M(n+)...pi complexes, the four DFT methods have been proven to be adequate in the prediction of these electrostatically stabilized systems, even though they tend to overestimate the interaction energies.
Physical Review E 09/2005; 72(2 Pt 2):026704. · 2.26 Impact Factor
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Computer Physics Communications. 01/2005; 169:335-338.
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ABSTRACT: Two alternative methods to relax the atomistic models of amorphous polymers generated by structure simulation (SuSi), a procedure recently developed that combines a generation algorithm and a minimization algorithm to localize independent energy minima (J. Chem. Phys. 2003, 119, 2915), are presented. These relaxation methods, which are based on the geometric aspects of the conventional configurational bias (CB) and concerted rotation (ConRot) Monte Carlo techniques, have been compared with the minimization algorithm originally implemented in SuSi. For this purpose, we considered two polymeric systems: four polyethylene chains with each one containing 400 CH2 groups and eight polyethylene chains with each one containing 800 CH2 groups. The procedure based on ConRot has been demonstrated to be the most efficient of the three relaxation algorithms, while the minimization one is the least efficient. On the other hand, the method based on CB is limited by the difficulties to relax the interior segments of chain molecules.
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Macromolecular Theory and Simulations 05/2004; 13(4):345 - 354. · 1.71 Impact Factor
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ABSTRACT: The performance of a recently developed method to generate representative atomistic models of amorphous polymers has been investigated. This method, which is denoted SuSi, can be defined as a random generator of energy minima. The effects produced by different parameters used to define the size of the system and the characteristics of the generation algorithm have been examined. Calculations have been performed on poly(L,D-lactic) acid (rho = 1.25 g/cm3) and nylon 6 (rho = 1.084 g/cm(3)), which are important commercial polymers.
Journal of Computational Chemistry 05/2004; 25(6):790-8. · 4.58 Impact Factor
