Juan Torras - Academia.edu (original) (raw)

Papers by Juan Torras

Research paper thumbnail of Close contacts at the interface: Experimental-computational synergies for solving complexity problems

Physical sciences reviews, Feb 15, 2018

The study of material science has been long devoted to the disentanglement of bulk structures whi... more The study of material science has been long devoted to the disentanglement of bulk structures which mainly entails finding the inner structure of materials. That structure is accountable for a major portion of materials' properties. Yet, as our knowledge of these "backbones" enlarged so did the interest for the materials' boundaries properties which means the properties at the frontier with the surrounding environment that is called interface. The interface is thus to be understood as the sum of the material's surface plus the surrounding environment be it in solid, liquid or gas phase. The study of phenomena at this interface requires both the use of experimental and theoretical techniques and, above all, a wise combination of them in order to shed light over the most intimate details at atomic, molecular and mesostructure levels. Here, we report several cases to be used as proof of concept of the results achieved when studying interface phenomena by combining a myriad of experimental and theoretical tools to overcome the usual limitation regardind atomic detail, size and time scales and systems of complex composition. Real world examples of the combined experimental-theoretical work and new tools, software, is offered to the readers.

Research paper thumbnail of Introduction to molecular modeling of materials in an undergraduate engineering degree

Research paper thumbnail of 2. Close Contacts at the interface: Experimental-computational synergies for solving complexity problems

De Gruyter eBooks, May 7, 2018

Research paper thumbnail of Recent Progress in Biomedical Sensors Based on Conducting Polymer Hydrogels

ACS applied bio materials, Apr 28, 2023

Research paper thumbnail of Hydrogels for flexible and compressible free standing cellulose supercapacitors

European Polymer Journal, Sep 1, 2019

Cellulose-based supercapacitors display important advantages in comparison with devices fabricate... more Cellulose-based supercapacitors display important advantages in comparison with devices fabricated with other materials, regarding environmental friendliness, flexibility, cost and versatility. Recent progress in the field has been mainly focused on the utilization of cellulose fibres as: structural mechanical reinforcement of electrodes; precursors of electrically active carbon-based materials; or primary electrolytes that act as reservoirs of secondary electrolytes. In this work, a flexible, lightweight, robust, portable and manageable all-carboxymethyl cellulose symmetric supercapacitor has been obtained by assembling two electrodes based on carboxymethyl cellulose hydrogels to a solid electrolytic medium formulated with the same material. Hydrogels, which were made by cross-linking carboxymethyl cellulose paste with citric acid in water, rendered not only effective solid electrolytic media by simply loading NaCl but also electroactive electrodes. For the latter, conducting polymer microparticles, which were loaded into the hydrogel network during the physical cross-linking step, were appropriately connected through the in situ anodic polymerization of a similar conducting polymer in aqueous medium, thus creating conduction paths. The performance of the assembled supercapacitors has been proved by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. This design opens a new window for the green and mass production of flexible cellulosebased supercapacitors.

Research paper thumbnail of Computer simulations on oxidative stress-induced reactions in SARS-CoV-2 spike glycoprotein: a multi-scale approach

Molecular Diversity, 2022

Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in... more Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in a misbalance of antioxidant and pro-oxidants species, is the common denominator of diseases considered as a risk factor for SARS-CoV-2 lethality. Indeed, reactive oxygen species caused by oxidative stress have been related to many virus pathogenicity. In this work, simulations have been performed on the receptor binding domain of SARS-CoV-2 spike glycoprotein to study what residues are more susceptible to be attacked by ·OH, which is one of the most reactive radicals associated to oxidative stress. The results indicate that isoleucine (ILE) probably plays a crucial role in modification processes driven by radicals. Accordingly, QM/MM-MD simulations have been conducted to study both the ·OH-mediated hydrogen abstraction of ILE residues and the induced modification of the resulting ILE radical through hydroxylation or nitrosylation reactions. All in all, in silico studies show the importa...

Research paper thumbnail of Free-Standing, Flexible Nanofeatured Polymeric Films Prepared by Spin-Coating and Anodic Polymerization as Electrodes for Supercapacitors

Molecules, 2021

Flexible and self-standing multilayered films made of nanoperforated poly(lactic acid) (PLA) laye... more Flexible and self-standing multilayered films made of nanoperforated poly(lactic acid) (PLA) layers separated by anodically polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) conducting layers have been prepared and used as electrodes for supercapacitors. The influence of the external layer has been evaluated by comparing the charge storage capacity of four- and five-layered films in which the external layer is made of PEDOT (PLA/PEDOT/PLA/PEDOT) and nanoperforated PLA (PLA/PEDOT/PLA/PEDOT/PLA), respectively. In spite of the amount of conducting polymer is the same for both four- and five-layered films, they exhibit significant differences. The electrochemical response in terms of electroactivity, areal specific capacitance, stability, and coulombic efficiency was greater for the four-layered electrodes than for the five-layered ones. Furthermore, the response in terms of leakage current and self-discharge was significantly better for the former electrodes than for the latter ones.

Research paper thumbnail of IgG1-b12HIV-gp120 Interface in Solution: A Computational Study

The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) ha... more The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) has been shown to be a promising therapeutic modality in the prevention of HIV infection. Understanding the b12−gp120 binding mechanism under physiological conditions may assist the development of more broadly effective antibodies. In this work, the main conformations and interactions between the receptorbinding domain (RBD) of spike glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated molecular dynamics (aMD) and ab initio hybrid molecular dynamics have been combined to determine the most persistent interactions between the most populated conformations of the antibody−antigen complex under physiological conditions. The results show the most persistent receptor-binding mapping in the conformations of the antibody−antigen interface in solution. The binding-free-energy decomposition reveals a small enhancement in the contribution played by the CDR-H3 region to the b12−gp120 interface compared to the crystal structure.

Research paper thumbnail of Poly(aspartic acid) Biohydrogel as the Base of a New Hybrid Conducting Material

International Journal of Molecular Sciences, 2021

In the present study, a composite made of conducting polymer, poly(3,4-ethylenedioxythiophene) (P... more In the present study, a composite made of conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), and a biodegradable hydrogel of poly(aspartic acid) (PASP) were electrochemically interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT) to prepare a new interpenetrated polymer network (IPN). Different cross-linker and PEDOT MPs contents, as well as different electropolymerization times, were studied to optimize the structural and electrochemical properties. The properties of the new material, being electrically conductive, biocompatible, bioactive, and biodegradable, make it suitable for possible uses in biomedical applications.

Research paper thumbnail of In silico antibody engineering for SARS-CoV-2 detection

Computational and Structural Biotechnology Journal, 2021

Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detectio... more Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detection elements in protein-based biosensors with clinical applications. The strategy usually employed for the de novo design of such engineered IgGs consists on merging fragments of the three-dimensional structure of a native IgG, which is immobilized on the biosensor surface, and of an antibody with an exquisite target specificity and affinity. In this work conventional and accelerated classical molecular dynamics (cMD and aMD, respectively) simulations have been used to propose two IgG-like antibodies for COVID-19 detection. More specifically, the crystal structure of the IgG1 B12 antibody, which inactivates the human immunodeficiency virus-1, has been merged with the structure of the antibody CR3022 Fab tightly bounded to SARS-CoV-2 receptor-binding domain (RBD) and the structure of the S309 antibody Fab fragment complexed with SARS-CoV-2 RBD. The two constructed antibodies, named IgG1-CR3022 and IgG1-S309, respectively, have been immobilized on a stable gold surface through a linker. Analyses of the influence of both the merging strategy and the substrate on the stability of the two constructs indicate that the IgG1-S309 antibody better preserves the neutralizing structure than the IgG1-CR3022 one. Overall, results indicate that the IgG1-S309 is appropriated for the generation of antibody based sensors for COVID-19 diagnosis.

Research paper thumbnail of Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein

Computational and Structural Biotechnology Journal, 2021

Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms... more Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.

Research paper thumbnail of Electroactive interpenetrated biohydrogels as hybrid materials based on conducting polymers

Journal of Applied Polymer Science, 2020

Different levels of interpenetration of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT) ... more Different levels of interpenetration of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT) inside a poly‐γ‐glutamic acid (γPGA) biohydrogel matrix, previously loaded with microparticles of poly(3,4‐ethylenedioxythiophene) (PEDOT), have been obtained. The degree of interpenetration has shown influence on the morphological and electrochemical properties of the resulting biohydrogel ([PEDOT/γPGA]PHMeDOT) with a maximum after 1 h of PHMeDOT polymerization time. The high biocompatibility of all biohydrogel components, together with the combination of mechanical properties of γPGA hydrogels with the electrochemical properties of interconnected microparticles of PEDOT, makes it a promising material for next generation of biosensors.

Research paper thumbnail of Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

A key factor for improving the sensitivity and performance of immunosensors based on mechanical-p... more A key factor for improving the sensitivity and performance of immunosensors based on mechanical-plasmonic methods is the orientation of the antibody proteins immobilized on the inorganic surface. Although experimental techniques fail to determine surface phenomena at the molecular level, modern simulations open the possibility of improving our understanding of protein-surface interactions. In this work, Replica Exchange Molecular Dynamics (REMD) simulations have been used to model the IgG1 protein tethered on amorphous silica surface considering a united-atom model and a relatively large system (2500 nm 2 surface). Additional Molecular Dynamics (MD) simulations have been conducted to derive an atomistic model for the amorphous silica surface using the cristobalite crystal structure as starting point and to examine the structure of the free IgG1 antibody in solution for comparison when immobilized. Analyses of the trajectories obtained for the tethered IgG1, which was sampled considering 32 different temperatures, have been used to define the geometry of the protein with respect to the inorganic surface. The tilt angle of the protein with respect to the surface plane increases with the temperature, the most populated value being 24º, and 66º and 87º at the lowest (250 K), room (298 K) and highest (380 K) temperature. This variation indicates that the importance of proteinsurface interactions decreases with increasing temperature. The influence of the surface on the structure of the antibody is very significant in the constant region, which is directly involved in the tethering process, while it is relatively unimportant for the antigen-binding fragments, which are farthest from the surface. These results are expected to contribute to the development of improved mechanical-plasmonic sensor microarrays in the near future.

Research paper thumbnail of Doped photo-crosslinked polyesteramide hydrogels as solid electrolytes for supercapacitors

Soft Matter, 2020

High-performance hydrogels play a crucial role as solid electrolytes for flexible electrochemical... more High-performance hydrogels play a crucial role as solid electrolytes for flexible electrochemical supercapacitors.

Research paper thumbnail of Study on the control of porosity in films of polythiophene derivatives

Polymer, 2019

Conducting polymers typically exhibit different oxidation states, which are easily interchangeabl... more Conducting polymers typically exhibit different oxidation states, which are easily interchangeable among them by means of the application of an electrical potential. In this work, we present a theoretical and experimental study to regulate the pore size of poly(3,4ethylenedioxythiophene) (PEDOT) films doped with ClO 4 ions by controlling their oxidation state. More specifically, different bulk and surface PEDOT models have been evaluated applying 2D-and 3-D periodic boundary conditions to density functional theory calculations. In highly oxidized PEDOT films, calculations predict that the incorporation of dopant ions increases the separation between neighboring chains, causing a structural reorganization. Thus, the calculated average pore size, which has been modeled as a structural defect in 2D surface models, increases by 15.1%. This increment is consistent with experimental measures of the nanopore size in PEDOT films with enhanced porosity, which reflect a difference of 25.2% between the oxidized and reduced forms. This superficial phenomenon could easily be used to retain and release controlled drugs through the application of different electric potentials.

Research paper thumbnail of The fully‐extended conformation in peptides and proteins

Peptide Science, 2018

The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and t... more The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. I...

Research paper thumbnail of Paradigm Shift for Preparing Versatile M(2+)-Free Gels from Unmodified Sodium Alginate

Biomacromolecules, Jan 28, 2017

This manuscript describes a new route to prepare rapidly Ca(2+)-free hydrogels from unmodified so... more This manuscript describes a new route to prepare rapidly Ca(2+)-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good poten...

Research paper thumbnail of Solvent effects on the properties of hyperbranched polythiophenes

Physical Chemistry Chemical Physics, 2016

The structural and electronic properties in solution of all-thiophene dendrimers and dendrons hav... more The structural and electronic properties in solution of all-thiophene dendrimers and dendrons have been evaluated using very different theoretical approaches based on quantum mechanical (QM) and hybrid QM/molecular mechanics (MM) methodologies: i) calculations on minimum energy conformations using an implicit solvation model combined with density functional theory (DFT) or time-dependent DFT methods (TD-DFT); ii) hybrid QM/MM calculations, in which the solute and solvent molecules are represented at the DFT level using as point charges, respectively, on snapshots extracted from classical molecular dynamics (MD) simulations with explicit solvent molecules; and iii) QM/MM-MD trajectories in which the solute is described at the DFT or TD-DFT level and the explicit solvent molecules are represented using classical force-fields. Calculations have been performed on dichloromethane, tetrahydrofurane and dimethylformamide. Comparison of the results obtained using the different approaches with available experimental data indicates that, the incorporation of effects associated to both the conformational dynamics of the dendrimer and the explicit solvent molecules is strictly necessary to satisfactorily reproduce the properties of the investigated systems. Accordingly, QM/MM-MD simulations are able to capture such effects providing a reliable description of electronic properties-conformational flexibility relationships in all-Th dendrimers.

Research paper thumbnail of Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)

International Journal of Molecular Sciences, 2021

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, pr... more Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target ce...

Research paper thumbnail of Cross-linking in polypyrrole and poly(N-methylpyrrole): Comparative experimental and theoretical studies

Polymer, 2008

A comparative study about cross-linking in electrogenerated polypyrrole and poly(N-methylpyrrole)... more A comparative study about cross-linking in electrogenerated polypyrrole and poly(N-methylpyrrole) is presented. Experimental studies on polymer films prepared under a constant potential of 1.4 V but considering different polymerization times as well as quantum mechanical calculations on model oligomers indicated that cross-linking is very low in polypyrrole, while cross-links are frequently formed by poly(N-methylpyrrole) chains. These behaviors have been attributed to the architecture of the molecular chains, which is completely different for the two systems under study. Thus, polypyrrole forms linear chains with some irregularities in the interring linkages, while branched molecules with many irregularities are the most stable for poly(N-methylpyrrole). These remarkable differences are fundamentally due to the steric repulsions induced by the methyl groups of poly(N-methylpyrrole).

Research paper thumbnail of Close contacts at the interface: Experimental-computational synergies for solving complexity problems

Physical sciences reviews, Feb 15, 2018

The study of material science has been long devoted to the disentanglement of bulk structures whi... more The study of material science has been long devoted to the disentanglement of bulk structures which mainly entails finding the inner structure of materials. That structure is accountable for a major portion of materials' properties. Yet, as our knowledge of these "backbones" enlarged so did the interest for the materials' boundaries properties which means the properties at the frontier with the surrounding environment that is called interface. The interface is thus to be understood as the sum of the material's surface plus the surrounding environment be it in solid, liquid or gas phase. The study of phenomena at this interface requires both the use of experimental and theoretical techniques and, above all, a wise combination of them in order to shed light over the most intimate details at atomic, molecular and mesostructure levels. Here, we report several cases to be used as proof of concept of the results achieved when studying interface phenomena by combining a myriad of experimental and theoretical tools to overcome the usual limitation regardind atomic detail, size and time scales and systems of complex composition. Real world examples of the combined experimental-theoretical work and new tools, software, is offered to the readers.

Research paper thumbnail of Introduction to molecular modeling of materials in an undergraduate engineering degree

Research paper thumbnail of 2. Close Contacts at the interface: Experimental-computational synergies for solving complexity problems

De Gruyter eBooks, May 7, 2018

Research paper thumbnail of Recent Progress in Biomedical Sensors Based on Conducting Polymer Hydrogels

ACS applied bio materials, Apr 28, 2023

Research paper thumbnail of Hydrogels for flexible and compressible free standing cellulose supercapacitors

European Polymer Journal, Sep 1, 2019

Cellulose-based supercapacitors display important advantages in comparison with devices fabricate... more Cellulose-based supercapacitors display important advantages in comparison with devices fabricated with other materials, regarding environmental friendliness, flexibility, cost and versatility. Recent progress in the field has been mainly focused on the utilization of cellulose fibres as: structural mechanical reinforcement of electrodes; precursors of electrically active carbon-based materials; or primary electrolytes that act as reservoirs of secondary electrolytes. In this work, a flexible, lightweight, robust, portable and manageable all-carboxymethyl cellulose symmetric supercapacitor has been obtained by assembling two electrodes based on carboxymethyl cellulose hydrogels to a solid electrolytic medium formulated with the same material. Hydrogels, which were made by cross-linking carboxymethyl cellulose paste with citric acid in water, rendered not only effective solid electrolytic media by simply loading NaCl but also electroactive electrodes. For the latter, conducting polymer microparticles, which were loaded into the hydrogel network during the physical cross-linking step, were appropriately connected through the in situ anodic polymerization of a similar conducting polymer in aqueous medium, thus creating conduction paths. The performance of the assembled supercapacitors has been proved by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. This design opens a new window for the green and mass production of flexible cellulosebased supercapacitors.

Research paper thumbnail of Computer simulations on oxidative stress-induced reactions in SARS-CoV-2 spike glycoprotein: a multi-scale approach

Molecular Diversity, 2022

Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in... more Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in a misbalance of antioxidant and pro-oxidants species, is the common denominator of diseases considered as a risk factor for SARS-CoV-2 lethality. Indeed, reactive oxygen species caused by oxidative stress have been related to many virus pathogenicity. In this work, simulations have been performed on the receptor binding domain of SARS-CoV-2 spike glycoprotein to study what residues are more susceptible to be attacked by ·OH, which is one of the most reactive radicals associated to oxidative stress. The results indicate that isoleucine (ILE) probably plays a crucial role in modification processes driven by radicals. Accordingly, QM/MM-MD simulations have been conducted to study both the ·OH-mediated hydrogen abstraction of ILE residues and the induced modification of the resulting ILE radical through hydroxylation or nitrosylation reactions. All in all, in silico studies show the importa...

Research paper thumbnail of Free-Standing, Flexible Nanofeatured Polymeric Films Prepared by Spin-Coating and Anodic Polymerization as Electrodes for Supercapacitors

Molecules, 2021

Flexible and self-standing multilayered films made of nanoperforated poly(lactic acid) (PLA) laye... more Flexible and self-standing multilayered films made of nanoperforated poly(lactic acid) (PLA) layers separated by anodically polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) conducting layers have been prepared and used as electrodes for supercapacitors. The influence of the external layer has been evaluated by comparing the charge storage capacity of four- and five-layered films in which the external layer is made of PEDOT (PLA/PEDOT/PLA/PEDOT) and nanoperforated PLA (PLA/PEDOT/PLA/PEDOT/PLA), respectively. In spite of the amount of conducting polymer is the same for both four- and five-layered films, they exhibit significant differences. The electrochemical response in terms of electroactivity, areal specific capacitance, stability, and coulombic efficiency was greater for the four-layered electrodes than for the five-layered ones. Furthermore, the response in terms of leakage current and self-discharge was significantly better for the former electrodes than for the latter ones.

Research paper thumbnail of IgG1-b12HIV-gp120 Interface in Solution: A Computational Study

The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) ha... more The use of broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) has been shown to be a promising therapeutic modality in the prevention of HIV infection. Understanding the b12−gp120 binding mechanism under physiological conditions may assist the development of more broadly effective antibodies. In this work, the main conformations and interactions between the receptorbinding domain (RBD) of spike glycoprotein gp120 of HIV-1 and the IgG1-b12 mAb are studied. Accelerated molecular dynamics (aMD) and ab initio hybrid molecular dynamics have been combined to determine the most persistent interactions between the most populated conformations of the antibody−antigen complex under physiological conditions. The results show the most persistent receptor-binding mapping in the conformations of the antibody−antigen interface in solution. The binding-free-energy decomposition reveals a small enhancement in the contribution played by the CDR-H3 region to the b12−gp120 interface compared to the crystal structure.

Research paper thumbnail of Poly(aspartic acid) Biohydrogel as the Base of a New Hybrid Conducting Material

International Journal of Molecular Sciences, 2021

In the present study, a composite made of conducting polymer, poly(3,4-ethylenedioxythiophene) (P... more In the present study, a composite made of conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), and a biodegradable hydrogel of poly(aspartic acid) (PASP) were electrochemically interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT) to prepare a new interpenetrated polymer network (IPN). Different cross-linker and PEDOT MPs contents, as well as different electropolymerization times, were studied to optimize the structural and electrochemical properties. The properties of the new material, being electrically conductive, biocompatible, bioactive, and biodegradable, make it suitable for possible uses in biomedical applications.

Research paper thumbnail of In silico antibody engineering for SARS-CoV-2 detection

Computational and Structural Biotechnology Journal, 2021

Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detectio... more Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detection elements in protein-based biosensors with clinical applications. The strategy usually employed for the de novo design of such engineered IgGs consists on merging fragments of the three-dimensional structure of a native IgG, which is immobilized on the biosensor surface, and of an antibody with an exquisite target specificity and affinity. In this work conventional and accelerated classical molecular dynamics (cMD and aMD, respectively) simulations have been used to propose two IgG-like antibodies for COVID-19 detection. More specifically, the crystal structure of the IgG1 B12 antibody, which inactivates the human immunodeficiency virus-1, has been merged with the structure of the antibody CR3022 Fab tightly bounded to SARS-CoV-2 receptor-binding domain (RBD) and the structure of the S309 antibody Fab fragment complexed with SARS-CoV-2 RBD. The two constructed antibodies, named IgG1-CR3022 and IgG1-S309, respectively, have been immobilized on a stable gold surface through a linker. Analyses of the influence of both the merging strategy and the substrate on the stability of the two constructs indicate that the IgG1-S309 antibody better preserves the neutralizing structure than the IgG1-CR3022 one. Overall, results indicate that the IgG1-S309 is appropriated for the generation of antibody based sensors for COVID-19 diagnosis.

Research paper thumbnail of Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein

Computational and Structural Biotechnology Journal, 2021

Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms... more Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.

Research paper thumbnail of Electroactive interpenetrated biohydrogels as hybrid materials based on conducting polymers

Journal of Applied Polymer Science, 2020

Different levels of interpenetration of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT) ... more Different levels of interpenetration of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT) inside a poly‐γ‐glutamic acid (γPGA) biohydrogel matrix, previously loaded with microparticles of poly(3,4‐ethylenedioxythiophene) (PEDOT), have been obtained. The degree of interpenetration has shown influence on the morphological and electrochemical properties of the resulting biohydrogel ([PEDOT/γPGA]PHMeDOT) with a maximum after 1 h of PHMeDOT polymerization time. The high biocompatibility of all biohydrogel components, together with the combination of mechanical properties of γPGA hydrogels with the electrochemical properties of interconnected microparticles of PEDOT, makes it a promising material for next generation of biosensors.

Research paper thumbnail of Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

A key factor for improving the sensitivity and performance of immunosensors based on mechanical-p... more A key factor for improving the sensitivity and performance of immunosensors based on mechanical-plasmonic methods is the orientation of the antibody proteins immobilized on the inorganic surface. Although experimental techniques fail to determine surface phenomena at the molecular level, modern simulations open the possibility of improving our understanding of protein-surface interactions. In this work, Replica Exchange Molecular Dynamics (REMD) simulations have been used to model the IgG1 protein tethered on amorphous silica surface considering a united-atom model and a relatively large system (2500 nm 2 surface). Additional Molecular Dynamics (MD) simulations have been conducted to derive an atomistic model for the amorphous silica surface using the cristobalite crystal structure as starting point and to examine the structure of the free IgG1 antibody in solution for comparison when immobilized. Analyses of the trajectories obtained for the tethered IgG1, which was sampled considering 32 different temperatures, have been used to define the geometry of the protein with respect to the inorganic surface. The tilt angle of the protein with respect to the surface plane increases with the temperature, the most populated value being 24º, and 66º and 87º at the lowest (250 K), room (298 K) and highest (380 K) temperature. This variation indicates that the importance of proteinsurface interactions decreases with increasing temperature. The influence of the surface on the structure of the antibody is very significant in the constant region, which is directly involved in the tethering process, while it is relatively unimportant for the antigen-binding fragments, which are farthest from the surface. These results are expected to contribute to the development of improved mechanical-plasmonic sensor microarrays in the near future.

Research paper thumbnail of Doped photo-crosslinked polyesteramide hydrogels as solid electrolytes for supercapacitors

Soft Matter, 2020

High-performance hydrogels play a crucial role as solid electrolytes for flexible electrochemical... more High-performance hydrogels play a crucial role as solid electrolytes for flexible electrochemical supercapacitors.

Research paper thumbnail of Study on the control of porosity in films of polythiophene derivatives

Polymer, 2019

Conducting polymers typically exhibit different oxidation states, which are easily interchangeabl... more Conducting polymers typically exhibit different oxidation states, which are easily interchangeable among them by means of the application of an electrical potential. In this work, we present a theoretical and experimental study to regulate the pore size of poly(3,4ethylenedioxythiophene) (PEDOT) films doped with ClO 4 ions by controlling their oxidation state. More specifically, different bulk and surface PEDOT models have been evaluated applying 2D-and 3-D periodic boundary conditions to density functional theory calculations. In highly oxidized PEDOT films, calculations predict that the incorporation of dopant ions increases the separation between neighboring chains, causing a structural reorganization. Thus, the calculated average pore size, which has been modeled as a structural defect in 2D surface models, increases by 15.1%. This increment is consistent with experimental measures of the nanopore size in PEDOT films with enhanced porosity, which reflect a difference of 25.2% between the oxidized and reduced forms. This superficial phenomenon could easily be used to retain and release controlled drugs through the application of different electric potentials.

Research paper thumbnail of The fully‐extended conformation in peptides and proteins

Peptide Science, 2018

The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and t... more The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. I...

Research paper thumbnail of Paradigm Shift for Preparing Versatile M(2+)-Free Gels from Unmodified Sodium Alginate

Biomacromolecules, Jan 28, 2017

This manuscript describes a new route to prepare rapidly Ca(2+)-free hydrogels from unmodified so... more This manuscript describes a new route to prepare rapidly Ca(2+)-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good poten...

Research paper thumbnail of Solvent effects on the properties of hyperbranched polythiophenes

Physical Chemistry Chemical Physics, 2016

The structural and electronic properties in solution of all-thiophene dendrimers and dendrons hav... more The structural and electronic properties in solution of all-thiophene dendrimers and dendrons have been evaluated using very different theoretical approaches based on quantum mechanical (QM) and hybrid QM/molecular mechanics (MM) methodologies: i) calculations on minimum energy conformations using an implicit solvation model combined with density functional theory (DFT) or time-dependent DFT methods (TD-DFT); ii) hybrid QM/MM calculations, in which the solute and solvent molecules are represented at the DFT level using as point charges, respectively, on snapshots extracted from classical molecular dynamics (MD) simulations with explicit solvent molecules; and iii) QM/MM-MD trajectories in which the solute is described at the DFT or TD-DFT level and the explicit solvent molecules are represented using classical force-fields. Calculations have been performed on dichloromethane, tetrahydrofurane and dimethylformamide. Comparison of the results obtained using the different approaches with available experimental data indicates that, the incorporation of effects associated to both the conformational dynamics of the dendrimer and the explicit solvent molecules is strictly necessary to satisfactorily reproduce the properties of the investigated systems. Accordingly, QM/MM-MD simulations are able to capture such effects providing a reliable description of electronic properties-conformational flexibility relationships in all-Th dendrimers.

Research paper thumbnail of Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)

International Journal of Molecular Sciences, 2021

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, pr... more Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target ce...

Research paper thumbnail of Cross-linking in polypyrrole and poly(N-methylpyrrole): Comparative experimental and theoretical studies

Polymer, 2008

A comparative study about cross-linking in electrogenerated polypyrrole and poly(N-methylpyrrole)... more A comparative study about cross-linking in electrogenerated polypyrrole and poly(N-methylpyrrole) is presented. Experimental studies on polymer films prepared under a constant potential of 1.4 V but considering different polymerization times as well as quantum mechanical calculations on model oligomers indicated that cross-linking is very low in polypyrrole, while cross-links are frequently formed by poly(N-methylpyrrole) chains. These behaviors have been attributed to the architecture of the molecular chains, which is completely different for the two systems under study. Thus, polypyrrole forms linear chains with some irregularities in the interring linkages, while branched molecules with many irregularities are the most stable for poly(N-methylpyrrole). These remarkable differences are fundamentally due to the steric repulsions induced by the methyl groups of poly(N-methylpyrrole).