Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation

Citation: Comer, J., Chen, R., Poblete, H., Vergara-Jaque, A., & Riviere, J. E. (2015). Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation. ACS Nano, 9(12), 11761–11774. https://doi.org/10.1021/acsnano.5b03592Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements. The calculations are highly predictive of the relative adsorption affinities of the compounds, with excellent correlation (r ? 0.9) between calculated and measured values of the logarithm of the adsorption equilibrium constant. Moreover, the agreement in absolute terms is also reasonable, with average errors of less than one decade. We also explore possible effects of surface loading, although we demonstrate that they are negligible for the experimental conditions considered. Given the degree of reliability demonstrated, we move on to employing the in silico techniques in the design of nanomaterials, using the optimization of adsorption affinity for the herbacide atrazine as an example. Our simulations suggest that, compared to other modifications of graphenic carbon, polyvinylpyrrolidone conjugation gives the highest affinity for atrazine—substantially greater than that of graphenic carbon alone—and may be useful as a nanomaterial for delivery or sequestration of atrazine

Propiedades estructurales y electrostaticas en la via de conduccion ionica del canal de potasio (K+) Shaker y los mutantes P475D y P475Q

87 p.Los canales de potasio (K+) dependientes de voltaje abren y cierran el poro en respuesta a cambios en el voltaje de la membrana, permitiendo asi­ la conduccion o no de iones a traves de la bicapa lipi­dica. Estos canales presentan una elevada selectividad al ion potasio, determinada por la secuencia aminoacídica TVGYGD altamente conservada entre los distintos canales de K+. De acuerdo a esto, la conductancia unitaria entre ellos deberi­a ser similar, sin embargo vari­a considerablemente entre un canal y otro. En el canal Shaker la secuencia PVP del segmento S6, forma una compuerta de entrada que se cierra ante un voltaje negativo de membrana, no obstante la mutacion de la segunda prolina por acido aspartico o glutamina (P475D o P475Q), bajo estas condiciones, muestra una conductancia ~10 y ~7 veces mayor a la del canal silvestre. El objetivo de este trabajo es determinar las propiedades estructurales y electrostaticas que gobiernan las variaciones en la conductancia entre el canal Shaker silvestre y los mutantes P475D y P475Q. Para realizar este estudio se utilizaron tecnicas de simulacion molecular, acompanadas de calculos de potencial electroestatico en la vi­a de conduccion ionica del canal. El analisis de las propiedades estructurales y electrostaticas correlacionadas con la conductancia, sugieren que el incremento de esta se debe a la presencia de un residuo polar, lo que provoca una perturbacion estructural de la compuerta de apertura y aumenta el potencial electrostatico en la cavidad interna del poro. La ausencia de la prolina 475 en el segmento S6 disminuye el angulo de quiebre de este segmento, aumentando el volumen del vestíbulo interno. De esta misma forma, la presencia de residuos polares incrementa el potencial electrostatico en la region PVP, generando un nuevo sitio de union a K+, lo que confiere una mayor estabilidad de estos iones, acelerando así la conducción iónica en la cavidad intracelular. Palabras Claves: Canal de Potasio - Shaker - Region PVP - Modelamiento Comparativo - Simulacion Molecular - Algoritmo HOLE - PMF - Potencial Electrostatico - Densidad ionica./ ABSTRACT: Voltage-gated potassium (Kv) channels open and close their ion-conduction pore in response to changes in membrane voltage, allowing the ions conduction through the lipid bilayer. These channels have a high selectivity over potassium ions, determined by the amino acid sequence TVGYGD, highly conserved among different K+ channels. According to this, the unitary conductance between these channels would be similar, however it varies considerably from one potassium channel to another. In Shaker potassium channels the PVP sequence in segment S6, forms an entrance gate that is closed in presence of a negative membrane voltage; Nevertheless, mutants of proline 475 to aspartic acid or glutamine (P475D or P475Q), under these conditions, show a conductance ~10 y ~7 times higher than the wild type channel. The goal of this study is to determine the structure and electrostatic properties responsible of the conductance differences between the Shaker wild type channel and the P475D and P475Q mutants. To perform this study, molecular simulation techniques and electrostatic potential calculations in the permeation pathway of Shaker were carried out. The analysis of the structural and electrostatic properties correlated with conductance data, shows that the increase of conductance is due to the presence of a polar residue, that causes a structural disruption of the intracellular entrance and increases the electrostatic potential in the pore internal cavity. The absence of proline 475 in the S6 segment decreases the angle of rupture of this segment, increasing the volume of intracellular aqueous cavity. In the same way, the presence of polar residues increase the electrostatic potential in the PVP region, generating a new K+ binding site, which confers a better stability for these ions, accelerating the ion conduction in the intracellular cavity

Efectos estructurales y energéticos de residuos críticos (Y671 Y K639) en la capacidad de transportar iones en el poro del canal receptor de potencial transitorio vaniloide tipo 1 (TRPV1)

87 p.El canal receptor de potencial transitorio vaniloide tipo 1 (TRPV1), es un integrador molecular de estímulos físicos y químicos en nociceptores periféricos.Este canal se destaca por participar en la percepción del dolor y la hipersensibilidad térmica durante procesos que involucran inflamación, por lo que es considerado un potencial blanco terapéutico para el desarrollo de fármacos anestésicos. Dentro de la estructura de TRPV1 han sido identificadas varias regiones y aminoácidos involucrados en funciones específicas del canal. De modo que, datos experimentales han mostrado que la mutación del residuo Tyr671 en el poro de TRPV1, por aminoácidos con propiedades fisicoquímicas diferentes altera la permeabilidad iónica del canal y su capacidad de desensibilización. A su vez, la neutralización del residuo K639 aumenta la inhibición por protones. Por lo que, mediante la utilización de metodologías bioinformáticas se analizó los efectos estructurales y energéticos que generan mutaciones en los residuos Y671 y K639. A partir de los resultados obtenidos, se logró establecer que las variaciones producidas en la conductancia de TRPV1, son el resultado principalmente de cambios en el potencial electrostático del poro, más que a la generación de barreras estéricas que afecte el paso de los iones./ABSTRACT: The transient receptor potential vanilloid type 1 (TRPV1) channel is a molecular integrator of physical and chemical stimuli in peripheral nociceptors. This channel is characterized by participating in pain perception and thermal hypersensitivity during processes involving inflammation, therefore it is considered a potential target for the development of anesthetic drugs.Within the structure of TRPV1 have been identified several regions and amino acids involved in specific functions of the channel, so as experimental data have shown that mutation of Tyr671 residue on TRPV1 pore, by amino acids with different physicochemical properties, alters the permeability to ions of the channel and its desensitization capacity. In turn, the K639 residue neutralization increases the inhibition by protons. Therefore, the structural and energetic effects residues were analized using bioinformatics methodologies by mutations in Y671 and K639. Based on the results obtained, it was possible to establish that variations produced in the conductance of TRPV1, occur mainly from changes in electrostatic potential of the pore, instead of steric barrier that affects the passage of ions

Virtual Screening of Plant Volatile Compounds Reveals a High Affinity of Hylamorpha elegans (Coleoptera: Scarabaeidae) Odorant-Binding Proteins for Sesquiterpenes From Its Native Host

Indexación: Web of ScienceHylamorpha elegans (Burmeister) is a native Chilean scarab beetle considered to be a relevant agricultural pest to pasture and cereal and small fruit crops. Because of their cryptic habits, control with conventional methods is difficult; therefore, alternative and environmentally friendly control strategies are highly desirable. The study of proteins that participate in the recognition of odorants, such as odorant-binding proteins (OBPs), offers interesting opportunities to identify new compounds with the potential to modify pest behavior and computational screening of compounds, which is commonly used in drug discovery, may help to accelerate the discovery of new semiochemicals. Here, we report the discovery of four OBPs in H. elegans as well as six new volatiles released by its native host Nothofagus obliqua (Mirbel). Molecular docking performed between OBPs and new and previously reported volatiles from N. obliqua revealed the best binding energy values for sesquiterpenic compounds. Despite remarkable divergence at the amino acid level, three of the four OBPs evaluated exhibited the best interaction energy for the same ligands. Molecular dynamics investigation reinforced the importance of sesquiterpenes, showing that hydrophobic residues of the OBPs interacted most frequently with the tested ligands, and binding free energy calculations demonstrated van der Waals and hydrophobic interactions to be the most important. Altogether, the results suggest that sesquiterpenes are interesting candidates for in vitro and in vivo assays to assess their potential application in pest management strategies.http://jinsectscience.oxfordjournals.org/content/16/1/3

Caracterización estructural de FCXTH 1 y FCXTH 2 asociados al desarrollo y maduración del fruto de Fragaria chiloensis (L). Duch.

78 p.La frutilla chilena (Fragaria chiloensis) surge como una nueva alternativa comercial, debido a sus excelentes características organolépticas. Su fruto es de rápido ablandamiento, reflejado en la alteración de la textura del fruto, que influye negativamente en la sobrevida de postcosecha y calidad, limitando su comercialización. Estudios previos han demostrado que el ablandamiento esta relacionado con la alteración de la pared celular, lo que corresponde a una serie de modificaciones de los polisacáridos que la componen. Los xiloglucanos (XG), polisacáridos abundantes en la pared celular, entrecruzan las microfibras de celulosa otorgándole rigidez a la pared. Se piensa que la modificación de las cadenas de XG estaría involucrada en la alteración observada en la pared, lo que resulta en el ablandamiento del fruto. La enzima xiloglucano endotransglicosilasa / hidrolasa (XTH) presente en todos los tejidos vegetales, presenta alta afinidad a xiloglucano y posee actividad endotransglicosilasa (XET), endohidrolasa (XEH), o ambas. En F. chiloensis se han identificado dos genes, que presentan alta similitud de secuencia con miembros de la familia de las XTH. Fc-XTH1, presenta alta acumulación de transcritos especialmente en fruto y Fc-XTH2 relacionado con los procesos vegetativos como el crecimiento de las hojas. Con el fin de aportar nuevos antecedentes en el proceso de ablandamiento del fruto, y obtener una perspectiva sobre el mecanismo de acción a nivel molecular de las enzimas FcXTH1 y FcXTH2, se realizó modelamiento comparativo para construir las estructuras de éstas enzimas. Además, se exploró la interacción de sustratos xiloglucano (XG) con la proteína, usando simulaciones de acoplamiento molecular. Ambas enzimas mostraron energías favorables de afinidad para sustratos XG, sin embargo, la estabilidad del complejo depende del estado de glicosilación de FcXTH. Simulaciones de dinámica molecular evidenciaron una marcada estabilidad de ambas proteínas al estar glicosiladas con 9 manosas (9m). La estabilidad de los complejos fue evaluada a través de cálculos de energía libre de unión con el método MM-GBSA. Los datos son congruentes con un probable papel de XTH durante el desarrollo y maduración del fruto./ABSTRACT: The chilean strawberry (Fragaria chiloensis) appears as a new commercial alternative, due to its excellent organoleptics. Fragaria chiloensis’s fruit with fast softening, which is reflected in the alteration of the texture of the fruit that affects negatively the survival and quality of the postharvest, restricting its merchandising. Previous studies have demonstrated that the softening is related to the alteration of the cell wall, which corresponds to modifications of the constituent polysaccharides. The xyloglucans(XG), abundant polysaccharides in the cell wall, crisscross microfibers of cellulose providing stiffness to the wall. This phenomenon could be due to that the modification of XG chains would be involved in the alteration observed in the wall, which results in softening of the fruit. The xyloglucan endotransglycosylase enzyme / hydrolase (XTH) present in all vegetables tissues, exhibits high affinity to xyloglucan and possesses endotransglycosylase actvity (XET),endohydrolase activity (XEH) , or both. In F. chiloensis have been identified two genes that show high similitude of sequence with members of the XTH family. Fc-XTH1, presents high accumulation of transcripts, especially in fruit and Fc-XTH2 is related to the vegetative processes such as leaf growth. With the purpose of providing new information in the process of fruit softening and obtaining a perspective about the mechanism of action to molecular level of enzymes FcXTH1 and FcXTH2, comparative modeling was performed to build the structures of these enzymes. Moreover, the interaction of xyloglucan (XG) substrates with the protein was explored, by using molecular Docking simulations. Both enzymes showed favorable energies of affinity for XG substrates. However, the stability of the complex depends on the state of FcXTH glycosylation. Molecular dynamics simulations showed a marked stability of both proteins by being glycosylated with 9 mannose (9m). The stability of the complexes was evaluated through calculations of binding free energy with the MM-GBSA method. The data are consistent with a probable role of XTH during development and the fruit ripening

Interacciones proteína-proteína asociadas a canales TRP: un protocolo computacional eficiente para la caracterización de macrocomplejos

59 p.Las interacciones proteína-proteína (PPIs) modulan una gran cantidad de funciones a nivel celular, logrando controlar procesos metabólicos, la regulación y expresión de proteínas en la membrana celular, entre otros fenómenos biológicos. Una asociación proteína-proteína corresponde a contactos físicos que pueden establecerse mediante interacciones electrostáticas e hidrofóbicas entre residuos superficiales que conforman la interfaz de unión de un complejo proteico. Existe evidencia de la formación de complejos proteína-proteína en miembros de la familia de canales iónicos Receptores de Potencial Transitorio (TRP). Específicamente, los canales de la subfamilia TRPC (canónicos o clásicos) han mostrado interactuar con proteínas externas denominadas “partners”, cuya asociación proteína-proteína podría modular procesos relacionados con enfermedades neurológicas y cardiacas. En el presente trabajo de tesis, se ha, caracterizado a nivel estructural la asociación del canal TRPC3 con la proteína 14-3-3η, cuya interacción se presume que regula el tráfico y expresión del canal en la membrana plasmática. A través de un análisis computacional, se determinaron las bases estructurales que gobiernan la interacción entre TRPC3 y 14-3-3η. Para ello, se utilizaron técnicas para la predicción de residuos de contacto en complejos proteína-proteína, protocolos de docking específicos para proteínas de membrana, dinámica molecular y cálculos de energía libre empleando modelos coarsegrained. A través de este estudio, se identificaron dos regiones de contacto entre las proteínas, las cuales pudieran ser posteriormente estudiadas en el contexto del diseño racional de fármacos para intervenir patologías relacionadas con la asociación de TRPC3 y 14-3-3η. // ABSTRACT: Protein-Protein Interactions (PPIs) modulate a large number of functions at the cellular level, controlling metabolic processes, the protein regulation and expression at the cell membrane, among other biological phenomena. The protein-protein association corresponds to physical contacts that can be established between proteins through electrostatic and hydrophobic interactions at the binding interface (hotspot) of a protein complex. There is evidence for the formation of protein-protein complexes in members of the Transient Receptor Potential (TRP) ion channel family. Specifically, channels of the TRPC subfamily (canonical or classical) have been shown to interact with external proteins called partners, whose protein-protein association could modulate processes related to neurological and cardiac diseases. In the present thesis work, the association of the TRPC3 channel with the 14-3-3η protein has been characterized at a structural level. This interaction is thought to regulate the traffic and expression of the channel at the plasma membrane. Through computational analyses, the structural bases modulating the interaction between TRPC3 and 14-3-3η were determined. To do that, techniques for the prediction of contact residues in protein-protein complexes, specific docking protocols for membrane proteins, molecular dynamics, and free energy calculations using coarse-grained models were used. Through this study, two contact regions between TRPC3 and 14-3-3η were identified, which could later be studied in the context of rational drug design to intervene related pathologies

Family resemblances: A common fold for some dimeric ion-coupled secondary transporters

Membrane transporter proteins catalyze the passage of a broad range of solutes across cell membranes, allowing the uptake and efflux of crucial compounds. Because of the difficulty of expressing, purifying, and crystallizing integral membrane proteins, relatively few transporter structures have been elucidated to date. Although every membrane transporter has unique characteristics, structural and mechanistic similarities between evolutionarily diverse transporters have been identified. Here, we compare two recently reported structures of membrane proteins that act as antimicrobial efflux pumps, namely MtrF from Neisseria gonorrhoeae and YdaH from Alcanivorax borkumensis, both with each other and with the previously published structure of a sodium-dependent dicarboxylate transporter from Vibrio cholerae, VcINDY. MtrF and YdaH belong to the p-aminobenzoyl-glutamate transporter (AbgT) family and have been reported as having architectures distinct from those of all other families of transporters. However, our comparative analysis reveals a similar structural arrangement in all three proteins, with highly conserved secondary structure elements. Despite their differences in biological function, the overall "design principle" of MtrF and YdaH appears to be almost identical to that of VcINDY, with a dimeric quaternary structure, helical hairpins, and clear boundaries between the transport and scaffold domains. This observation demonstrates once more that the same secondary transporter architecture can be exploited for multiple distinct transport modes, including cotransport and antiport. Based on our comparisons, we detected conserved motifs in the substrate-binding region and predict specific residues likely to be involved in cation or substrate binding. These findings should prove useful for the future characterization of the transport mechanisms of these families of secondary active transporters

Cambios conformacionales en proteínas transportadoras de membrana definidos por repeticiones de topología invertida

60 p.Los transportadores activos secundarios son proteínas transmembranales que median el paso de una amplia gama de solutos a través de la membrana lipídica. El proceso de transporte se basa en un mecanismo de acceso alternado que alcanza al menos tres estados distintivos: una conformación orientada al medio interno, otra conformación intermedia ocluida y una conformación orientada al medio externo. Pese a estos tres posibles estados conformacionales, las proteínas transportadoras tienden a cristalizar en un solo estado. El protocolo denominado “modelado por homología usando repeticiones de intercambio" permite actualmente estimar la conformación opuesta de un transportador usando como templado su conformación inversa. En el presente estudio se utilizó este protocolo para modelar el transportador de nitrato NRT1.1 de Arabidopsis thaliana perteneciente a la familia NPF en una conformación orientada hacia el medio externo. Posteriormente, sobre la base de la estructura cristalográfica de NRT1.1 y el modelo generado en una conformación inversa, se construyeron modelos comparativos de tres simportadores de H+/glucosinolato (GTR1, GTR2 y GTR3). A través de un análisis estructural de estas proteínas se logró identicar elementos claves para el transporte de nutrientes en proteínas transportadoras de plantas. Adicionalmente, se identicaron residuos implicados en la especificidad y translocación de sustratos. Los resultados obtenidos a lo largo de esta investigación sugieren un sitio de unión a glucosinolatos dependiente de su cadena lateral y predicen mutaciones claves para un transporte selectivo de nutrientes. // ABSTRACT: Secondary active transporters are transmembrane proteins that allow the passage of a wide range of solutes across the lipid membrane. The transport process is based on an alternate access mechanism that reaches at least three distinctive states: inward-facing, occluded and outward-facing conformation. Despite these three possible conformational states, membrane protein transporters tend to crystallize in a single state. The protocol called Repeat swap homology modelling currently allows estimating the opposite conformation of a transporter using its inverse conformation as template. In the present study, this protocol was used to model the nitrate transporter NRT1.1 of Arabidopsis thaliana belonging to the NPF family in an inward-facing conformation. Subsequently, on the basis of the crystallographic structure of NRT1.1 and the model generated in an inverse conformation, comparative models of three H+/glucosinolate symporters (GTR1, GTR2 and GTR3) were constructed. Through a structural analysis of these proteins, it was possible to identify key elements for the transport of nutrients in plant transport proteins. Additionally, residues involved in the specicity and translocation of substrates were identied. The results obtained in this investigation suggest a substrate binding site in the three transporters dependent on the glucosinolate's side chains and predict key mutations for selective nutrient transport

Análisis del interactoma de la proteína KCTD5 mediante la plataforma web PPI-MASS

53 p.Existe una gran cantidad de enfermedades humanas que han sido vinculadas a interacciones proteína-proteína (PPIs). El interactoma humano se compone de más de 600.000 complejos proteicos, los cuales se asocian a una gran diversidad de procesos celulares fundamentales para el correcto funcionamiento y desarrollo del organismo. Un caso de especial interés es el interactoma de la proteína KCTD5, la cual ha mostrado regular canales iónicos y estar asociada con cáncer de mama y la formación de ciertos tumores. Una manera de estudiar proteínas que regulan la función de KCTD5 es mediante ensayos de espectrometría de masas (MS); sin embargo, el post-procesamiento de datos resultantes de MS no es trivial y actualmente existen limitadas herramientas informáticas que brinden al usuario flexibilidad y transparencia para manejar e interpretar los datos. En este sentido, el presente proyecto de tesis describe el desarrollo de una plataforma web para el análisis de datos obtenidos a través de experimentos de MS, integrando información de diferentes bases de datos biológicas y permitiendo al usuario emplear determinados filtros para identificar complejos proteína-proteína con potencial farmacológico. El desempeño de la plataforma PPI-MASS, ha sido inicialmente evaluado usando como parámetros de entrada datos de MS vinculados a la proteína KCTD5. Sin embargo, se prevé su uso para el análisis y detección de cualquier conjunto de PPIs proveniente de experimentos de MS. Cabe señalar, que la detección de PPIs es fundamental para el diseño de fármacos basado en estructura, por lo tanto, se espera que esta plataforma sea un gran aporte en el área biomédica. //ABSTRACT: A large number of human diseases have been linked to protein-protein interactions (PPIs). The human interactome comprises over 600.000 protein complexes, which are associated with a wide variety of cell processes essential for the correct function and development of the human organism. One case of particular interest is the KCTD5 protein interactome. KCTD5 has been shown to regulate ion channels and to be associated with breast cancer and the formation of certain tumors. One way of studying the proteins that regulate the function of KCTD5 is through mass-spectrometry assays (MS); however, the post-processing of the resulting data is not a trivial task. Moreover, there are currently few computational tools that give the user flexibility and transparency to manage and interpret the data. In that regard, this thesis project describes the development of a web platform for the analysis of data obtained through MS assays, incorporating information from different biological databases and allowing the user to employ specific filters to identify protein-protein complexes with pharmaceutical potential. The performance of the PPI-MASS platform has been initially evaluated using MS data associated with the KCTD5 protein as input. However, we expect its use to analyze and detect any set of PPIs from MS assays. It is important to note that the detection of PPIs is essential for structure-based drug design and, because of this, we expect that this platform will be of great assistance in the biomedical field

Estudio computacional de la afinidad de dendrímeros PAMAN G0 por iones metálicos presentes en aguas contaminada

80 p.Los nanopolímeros dendríticos han sido potenciados en diversos ámbitos, siendo uno de ellos la remoción de metales en agua. Estos materiales presentan afinidad por diversas moléculas dependiendo de su grupo terminal que es capaz de modificar la especificidad de atrapamiento por ciertas moléculas. En esta tesis, se utilizaron aproximaciones químico-computacionales aplicadas al estudio de las interacciones entre metales y dendrímeros PAMAM G0 sin funcionalizar y funcionalizados con un conjunto de grupos terminales (asparagina, lisina y arginina). Los metales estudiados son iones bivalentes Cu, Ni y Zn que se presentan comúnmente como residuos tóxicos en agua. Las metodologías computacionales utilizadas corresponden a aproximaciones DTF (Teoría de Funcionales de la Densidad) y semi-empíricas. Los métodos utilizados permitieron recabar información relevante con respecto a la geometría y afinidad de éstos complejos. Los resultados obtenidos por medio de técnicas computacionales de la TFD indican que las coordinaciones más estables entre dendrímero-metal se encuentran en el sector del núcleo del dendrímero, para lo cual se obtuvieron geometrías del tipo cuadrado planar distorsionadas. Por otra parte, la afinidad encontrada por dichos estudios indica el siguiente orden: Ni(II) > Cu(II) > Zn(II), lo cual difiere de la información obtenida experimentalmente, la cual mostró la tendencia Cu(II) > Ni(II) y Zn(II). Sin embargo, estos estudios podrían ser complementados adicionando solvente implícito al sistema, lo que podría conseguir la misma tendencia en ambos estudios. Los cálculos por métodos semi-empíricos por su parte sugieren que se obtendría una mejor extracción de éstos metales a través de una funcionalización de PAMAM G0 con el grupo asparagina./ABSTRACT: Dendritic nanopolymers have been successfully applied in different technological solutions; one of them is the removal of metals in water. Dendrimers exhibit high affinity for different molecules depending of their terminal groups that are capable of modifying the capture specificity for certain molecules. In this thesis, computational chemistry approaches were used to study the interactions between metals and the non-functionalized dendrimer PAMAM G0, and PAMAM G0 functionalized with a set of chemical groups (asparagine, lysine and arginine). The selected metal ions corresponded to the divalent cations Cu, Ni and Zn, commonly present as toxic waste in water. Relevant information about the geometry and affinity of these metal complexes was obtained through DFT and semi-empirical approximations. DFT results indicated that the core area of the dendrimer corresponds to the most stable coordination site exhibiting a distorted square planar geometry. Moreover, the affinity of the ligand for each metal showed the following tendency: Ni(II)> Cu(II)> Zn(II). This sequence differs from the experimental information; however, the introduction of implicit solvation models could complement and improve these studies. Analyses of the complexation of metals with the functionalized dendrimer at semi-empirical level of theory showed that PAMAM G0 modified with asparagine is the best candidate for water remediatio