Multiple active zones in hybrid QM/MM molecular dynamics simulations for large biomolecular systems

A new QM/MM molecular dynamics approach that can deal with the dynamics of large real systems involving several simultaneous active zones is presented. Multiple, unconnected but interacting quantum regions are treated independently in an ordinary QM/MM approach but in a manner which converges to a unique simulation. The multiple active zones in the hybrid QM/MM molecular dynamics methodology (maz-QM/MM MD) involve molecular dynamics that is driving the whole simulation with several parallel executions of energy gradients within the QM/MM approach that merge into each MD step. The Ewald-summation method is used to incorporate long-range electrostatic interactions among the active zones in conjunction with periodic boundary conditions. To illustrate and ascertain capabilities and limitations, we present several benchmark calculations using this approach. Our results show that the maz-QM/MM MD method is able to provide simultaneous treatment of several active zones of very large proteins such as the Cu-4His-¿C* cage, a self-assembly of a 24-mer cage-like protein ferritinPeer ReviewedPostprint (published version

Solvent effects on the properties of hyperbranched polythiophenes

The structural and electronic properties of all-thiophene dendrimers and dendrons in solution 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 in combination with density functional theory (DFT) or time-dependent DFT (TD-DFT) methods; (ii) hybrid QM/MM calculations, in which the solute and solvent molecules are represented at the DFT level as point charges, respectively, on snapshots extracted from classical molecular dynamics (MD) simulations using 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 in dichloromethane, tetrahydrofuran and dimethylformamide. A comparison of the results obtained using the different approaches with the available experimental data indicates that the incorporation of effects associated with 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.Peer ReviewedPostprint (author's final draft

Massive quantum regions for simulations on bio-nanomaterials: synthetic ferritin nanocages

QM/MM molecular dynamics simulations on the 4His-DC* protein cage have been performed using multiple active zones (up to 86 quantum regions). The regulation and nanocage stability exerted by the divalent transitionmetal ions in the monomer-to-cage conversion have been understood by comparing high level quantum trajectories obtained using Cu2+ and Ni2+ coordination ions.Peer ReviewedPostprint (published version

Introduction to molecular modeling of materials in an undergraduate engineering degree

Molecular modeling is a chemistry tool that has been widely used in the last decades to mainly support the basic concepts of general chemistry and organic chemistry, in both undergraduate programs of basic sciences and some technological careers. Despite its use, except in some very specific cases, it has been extensively employed as illustrative examples of the chemical concepts that were being demonstrated. Despite the numerous existing applications to comprehend the phenomena behind the development of new materials and biomedicine, it is difficult to find a conceptual introduction of molecular modeling applied to specific problems on the modern engineeries within the undergraduate programs. In the present work, it will be shown the introduction and adaptation of molecular modeling concepts within a new optional course for students coming from materials engineering, chemical engineering and biomedicine engineeries. Different approaches to problem-based and small project-based learning are presented to encourage the scientific spirit of students using techniques of molecular modeling that had not been visited throughout their studies and, thus, to discover their potential appliacation in a more specialized context

Molecular dynamics study on the Apo- and Holo-forms of 5-lipoxygenase

Lipoxygenases (LOXs) are nonheme iron-containing enzymes catalyzing the dioxygenation of polyunsaturated fatty acids. LOX catalytic activity depends on the presence of iron in the active site and the iron removal is also able to affect the membrane binding properties of the enzyme. Leukotrienes biosynthesis is initiated by the action of 5-LOX at the level of nuclear membrane and the mechanism of enzyme-membrane interaction is thought to involve structural flexibility and conformational changes at the level of the protein tertiary structure. In this study, we have analyzed by molecular dynamics simulations the conformational changes induced by iron removal in 5-LOX. The data indicate that the degree of enzyme flexibility is related to the presence of iron into the active site that is able to stabilize the protein increasing its rigidity. These findings provide further evidence that the conformation and the functional activity of LOXs is tuned by the presence of iron at the active site, suggesting new approaches for the design of enzyme inhibitors.Peer ReviewedPostprint (author's final draft

Study on the control of porosity in films of polythiophene derivatives

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(3,4-ethylenedioxythiophene) (PEDOT) films doped with ClO4- 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 re-organization. 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 potentialsPeer ReviewedPostprint (author's final draft

Object modeling using a ToF camera under an uncertainty reduction approach

Trabajo presentado al ICRA 2010 celebrado en Anchorage (Alaska) del3 al 7 de mayo.Time-of-Flight (ToF) cameras deliver 3D images at 25 fps, offering great potential for developing fast object modeling algorithms. Surprisingly, this potential has not been extensively exploited up to now. A reason for this is that, since the acquired depth images are noisy, most of the available registration algorithms are hardly applicable. A further difficulty is that the transformations between views are in general not accurately known, a circumstance that multi-view object modeling algorithms do not handle properly under noisy conditions. In this work, we take into account both uncertainty sources (in images and camera poses) to generate spatially consistent 3D object models fusing multiple views with a probabilistic approach. We propose a method to compute the covariance of the registration process, and apply an iterative state estimation method to build object models under noisy conditions.This work was supported by projects: 'Perception, action & cognition through learning of object-action complexes.' (4915), 'CONSOL IDER-INGENIO 2010 Multimodal interaction in pattern recognition and computer vision' (V-00069), 'Percepción y acción ante incertidumbre' (4803). This work has been partially supported by the Spanish Ministry of Science and Innovation under project DPI2008-06022, the MIPRCV Consolider Ingenio 2010 project, and the EU PACO PLUS project FP6-2004-IST-4-27657. S. Foix and G. Alenyà are supported by PhD and postdoctoral fellowships, respectively, from CSIC’s JAE program.Peer Reviewe

Controlled Gaussian Process Dynamical Models with Application to Robotic Cloth Manipulation

Over the last years, robotic cloth manipulation has gained relevance within the research community. While significant advances have been made in robotic manipulation of rigid objects, the manipulation of non-rigid objects such as cloth garments is still a challenging problem. The uncertainty on how cloth behaves often requires the use of model-based approaches. However, cloth models have a very high dimensionality. Therefore, it is difficult to find a middle point between providing a manipulator with a dynamics model of cloth and working with a state space of tractable dimensionality. For this reason, most cloth manipulation approaches in literature perform static or quasi-static manipulation. In this paper, we propose a variation of Gaussian Process Dynamical Models (GPDMs) to model cloth dynamics in a low-dimensional manifold. GPDMs project a high-dimensional state space into a smaller dimension latent space which is capable of keeping the dynamic properties. Using such approach, we add control variables to the original formulation. In this way, it is possible to take into account the robot commands exerted on the cloth dynamics. We call this new version Controlled Gaussian Process Dynamical Model (C-GPDM). Moreover, we propose an alternative kernel representation for the model, characterized by a richer parameterization than the one employed in the majority of previous GPDM realizations. The modeling capacity of our proposal has been tested in a simulated scenario, where C-GPDM proved to be capable of generalizing over a considerably wide range of movements and correctly predicting the cloth oscillations generated by previously unseen sequences of control actions

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

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 importance of the chemical environment triggered by oxidative stress on the modifications of the virus, which is expected to help for foreseeing the identification or development of antioxidants as therapeutic drugs. Graphic abstrac

A study of tensile and bending properties of 3D-printed biocompatible materials used in dental appliances

In the last years, a large number of new biocompatible materials for 3D printers have emerged. Due to their recent appearance and rapid growth, there is little information about their mechanical properties. The design and manufacturing of oral appliances made with 3D printing technologies require knowledge of the mechanical properties of the biocompatible material used to achieve optimal performance for each application. This paper focuses on analyzing the mechanical behaviour of a wide range of biocompatible materials using different additive manufacturing technologies. To this end, tensile and bending tests on different types of recent biocompatible materials used with 3D printers were conducted to evaluate the influence of the material, 3D printing technology, and printing orientation on the fragile/ductile behaviour of the manufactured devices. A test bench was used to perform tensile tests according to ASTM D638 and bending tests according to ISO 178. The specimens were manufactured with nine different materials and five manufacturing technologies. Furthermore, specimens were created with different printing technologies, biocompatible materials, and printing orientations. The maximum allowable stress, rupture stress, flexural modulus, and deformation in each of the tested specimens were recorded. Results suggest that specimens manufactured with Stereolithography (SLA) and milling (polymethyl methacrylate PMMA) achieved high maximum allowable and rupture stress values. It was also observed that Polyjet printing and Selective Laser Sintering (SLS) technologies led to load-displacement curves with low maximum stress and high deformation values. Specimens manufactured with Digital Light Processing (DLP) technology showed intermediate and homogeneous performance. Finally, it was observed that the printing direction significantly influences the mechanical properties of the manufactured specimens in some cases.Universidad de Málag