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Una empresa sostenible es aquella que busca crear valor medioambiental, social y económico a corto, mediano y largo plazo, buscando así un impacto positivo al bienestar y al progreso de las presentes y futuras generaciones. El diagnóstico del nivel de sostenibilidad en las empresas del sector gastronómico del municipio de Olocuilta, pertenecientes específicamente al pupusódromo “El Manguito”, tiene como objetivo evaluar las micro y pequeñas empresas, con base en indicadores generalizados orientados a medir el nivel de sostenibilidad actual de las mismas. Se realizó una investigación de carácter exploratorio, en la cual se emplearon encuestas y se realizaron entrevistas, se recopiló información referente a los tres factores que integran el marco de la sostenibilidad. Los resultados obtenidos demuestran que existe una gran fortaleza a nivel económico y oportunidades de mejora social y medioambiental. Realidad Empresarial No. 8, 2019: 12-19

Na+/H+ exchangers catalyse an ion-exchange activity that is carried out in most, if not all cells. SLC9B2, also known as NHA2, correlates with the long-sought after sodium/lithium (Na+/Li+) exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite its functional importance, structural information and the molecular basis of its ion-exchange mechanism have been lacking. Here, we report the cryo EM structures of bison NHA2 in detergent and in nanodiscs at 3.0 and 3.5 Å resolution, respectively. NHA2 shares closest structural similarity to the bacterial electrogenic Na+/H+ antiporter NapA, rather than other mammalian SLC9A members. Nevertheless, SSM-based electrophysiology results with NHA2 show the catalysis of electroneutral rather than electrogenic ion exchange, and the ion-binding site is quite distinctive, with a tryptophan-arginine- glutamate triad separated from the well-established ion-binding aspartates. These triad residues fine-tune ion binding specificity, as demonstrated by a salt-bridge swap mutant that converts NHA2 into a Li+-specific transporter. Strikingly, an additional N-terminal helix in NHA2 establishes a unique homodimer with a large ∼ 25 Å intracellular gap between protomers. In the presence of phosphatidylinositol lipids, the N-terminal helix rearranges and closes this gap. We confirm that dimerization of NHA2 is required for activity in vivo, and propose that the N- terminal helix has evolved as a lipid-mediated remodelling switch for regulation of transport activity.

The Na

Na+/H+ exchangers (NHEs) are ancient membrane‐bound nanomachines that work to regulate intracellular pH, sodium levels and cell volume. NHE activities contribute to the control of the cell cycle, cell proliferation, cell migration and vesicle trafficking. NHE dysfunction has been linked to many diseases, and they are targets of pharmaceutical drugs. Despite their fundamental importance to cell homeostasis and human physiology, structural information for the mammalian NHE was lacking. Here, we report the cryogenic electron microscopy structure of NHE isoform 9 (SLC9A9) from Equus caballus at 3.2 Å resolution, an endosomal isoform highly expressed in the brain and associated with autism spectrum (ASD) and attention deficit hyperactivity (ADHD) disorders. Despite low sequence identity, the NHE9 architecture and ion‐binding site are remarkably similar to distantly related bacterial Na+/H+ antiporters with 13 transmembrane segments. Collectively, we reveal the conserved architecture of the NHE ion‐binding site, their elevator‐like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications., Cryo‐EM structures reveal conserved architecture and exchange mechanism of the horse endosomal Na+/H+ exchanger NHE9.

Ionizing radiation (IR) and chemotherapy are standard of care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knock-in mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.

Elucidating the mechanism of sugar import requires a molecular understanding of how transporters couple sugar binding and gating events. Whereas mammalian glucose transporters (GLUTs) are specialists1, the hexose transporter from the malaria parasite Plasmodium falciparum PfHT12,3 has acquired the ability to transport both glucose and fructose sugars as efficiently as the dedicated glucose (GLUT3) and fructose (GLUT5) transporters. Here, to establish the molecular basis of sugar promiscuity in malaria parasites, we determined the crystal structure of PfHT1 in complex with d-glucose at a resolution of 3.6 A. We found that the sugar-binding site in PfHT1 is very similar to those of the distantly related GLUT3 and GLUT5 structures4,5. Nevertheless, engineered PfHT1 mutations made to match GLUT sugar-binding sites did not shift sugar preferences. The extracellular substrate-gating helix TM7b in PfHT1 was positioned in a fully occluded conformation, providing a unique glimpse into how sugar binding and gating are coupled. We determined that polar contacts between TM7b and TM1 (located about 15 A from d-glucose) are just as critical for transport as the residues that directly coordinate d-glucose, which demonstrates a strong allosteric coupling between sugar binding and gating. We conclude that PfHT1 has achieved substrate promiscuity not by modifying its sugar-binding site, but instead by evolving substrate-gating dynamics. Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.

EGFR mutations display striking organ-site asymmetry and heterogeneity. We have shown that structurally diverse extracellular mutations, typical of glioblastomas, converge to a similar intermediate conformation, which can be synergistically targeted extra- and intracelullarly by antibody mAb806 and type-II kinase inhibitors. Our findings reveal convergence behind heterogeneity, paving the way for allostery-based co-targeting.

Proceedings of the National Academy of Sciences of the United States of America 116(20), 201821442 - (2019). doi:10.1073/pnas.1821442116, Epidermal growth factor receptor (EGFR) signaling is initiated by a large ligand-favored conformational change of the extracellular domain (ECD) from a closed, self-inhibited tethered monomer, to an open untethered state, which exposes a loop required for strong dimerization and activation. In glioblastomas (GBMs), structurally heterogeneous missense and deletion mutations concentrate at the ECD for unclear reasons. We explore the conformational impact of GBM missense mutations, combining elastic network models (ENMs) with multiple molecular dynamics (MD) trajectories. Our simulations reveal that the main missense class, located at the I-II interface away from the self-inhibitory tether, can unexpectedly favor spontaneous untethering to a compact intermediate state, here validated by small-angle X-ray scattering (SAXS). Significantly, such intermediate is characterized by the rotation of a large ECD fragment (N-TR1), deleted in the most common GBM mutation, EGFRvIII, and that makes accessible a cryptic epitope characteristic of cancer cells. This observation suggested potential structural equivalence of missense and deletion ECD changes in GBMs. Corroborating this hypothesis, our FACS, in vitro, and in vivo data demonstrate that entirely different ECD variants all converge to remove N-TR1 steric hindrance from the 806-epitope, which we show is allosterically coupled to an intermediate kinase and hallmarks increased oncogenicity. Finally, the detected extraintracellular coupling allows for synergistic cotargeting of the intermediate with mAb806 and inhibitors, which is proved herein., Published by National Acad. of Sciences, Washington, DC

Mapping pH-Dependent State Transitions of a Pentameric Ligand-gated Ion Channel through Markov State Modeling

Allosteric Gating Determinants in the Transmembrane Domain of Pentameric Ligand-Gated Ion Channels

Summary Understanding how proteins transition between different conformers, and how conformers relate to each other in terms of structure and function, is not trivial. Here, we present an online tool for transition pathway generation between two protein conformations using Elastic Network Driven Brownian Dynamics Importance Sampling, a coarse-grained simulation algorithm, which spontaneously predicts transition intermediates trapped experimentally. In addition to path-generation, the server provides an interactive 2D-motion landscape graphical representation of the transitions or any additional conformers to explore their structural relationships. Availability and implementation eBDIMS is available online: http://ebdims.biophysics.se/ or as standalone software: https://github.com/laura-orellana/eBDIMS, https://github.com/cabergh/eBDIMS. Supplementary information Supplementary data are available at Bioinformatics online.

Allosteric Modulation via Transmembrane Interfaces in a Pentameric Ligand-Gated Ion Channel

La presente tesis trata de aproximarse a las características del dibujo infantil de niños/as con Trastorno del Espectro del Autismo (TEA). Para ello hemos contado con veintitrés participantes de entre 4 y 12 años de diferentes colegios de la Provincia de Castellón, los cuales han elaborado cada uno un dibujo espontáneo, dos dibujos de figuras humanas y cinco dibujos del natural, que forman la muestra de la investigación. La metodología utilizada ha sido el estudio de casos, donde se analizan en profundidad los dibujos obtenidos de los participantes. Además de ello, también se han estudiado relaciones significativas entre estas variables y la sintomatología básica del TEA. Los resultados obtenidos aportan información acerca de los diversos aspectos estudiados en los dibujos de los participantes con autismo. A partir de estos, se proponen recomendaciones para tener en cuenta a la hora de elaborar pictogramas o imágenes dirigidas a esta población., This thesis tries to approach the characteristics of drawings made by children with Autism Spectrum Disorder (ASD). To do this, we worked with twenty-three participants between 4 and 12 years old from different schools in the Province of Castellón. Each one of them produced a spontaneous drawing, two drawings of human figures and five drawings of the natural, which form the sample of the investigation. The methodology used was a case study, where the drawings obtained from the participants are analysed in depth. In addition, significant relationships between these variables and the basic symptomatology of ASD have also been studied. The results obtained provide information about the various aspects studied in the drawings of participants with autism. From these, a series of recommendations are proposed to be taken into account when elaborating pictograms or images directed to this population.

Las tasas de prevalencia en el Trastorno del Espectro del Autismo (TEA) van en aumento, por lo que existe la necesidad de investigar acerca del mismo para mejorar en la comprensión de las características de las personas con autismo. Con lo que al ámbito de estudio de la educación artística se refiere, pocos estudios hay realizados que analicen aspectos del dibujo infantil en niños/as con TEA. Por ello, este artículo forma parte de un estudio de tesis doctoral, que analiza las características del dibujo infantil en niños/as con autismo. En el presente estudio se exponen los resultados obtenidos en relación a la temática infantil del dibujo espontáneo en niños/as con TEA. Prevalence rates in Autism Spectrum Disorder (ASD) are increasing, so there is a need to investigate about it to improve the understanding of the characteristics of people with autism. Thus the field of study of art education is concerned, there are few studies conducted to analyze aspects of the drawings of children with ASD. Therefore, this article is part of a study of PHD, which analyzes the characteristics of children's drawing with autism. In the present study we present the results obtained in relation to child theme of spontaneous drawing of children with ASD.

Background The reported data of HIV + pregnant women in Latin America (LA) is scarce. Given the political and social changes that have occurred in recent years, Chile has had to face immigration as a recent phenomenon. Based on this, the objective of this analysis was to determine the baseline characteristics, virological during pregnancy and postpartum, and the impact of immigration on adult women infected with HIV Methods The registry of HIV + pregnant women of Fundación Arriarán was analyzed since 2006. The baseline characteristics,undetectability at delivery, vertical transmission and retention were determined.Estimators as mean and median,standard deviation and interquartile range; absolute and relative frequencies were used and for the bivariate analysis the t-test and chi2,Mann–Whitney and Fisher’s exact. For follow-up, the Kaplan–Meier method was used. Results A total of 214 pregnancies in 198 HIV + women were included. A 54% of foreigners (of Haitian predominance) was found, 2/3 of the foreigners were enrolled after 2016. A 73% was diagnosed with HIV at the time of pregnancy. Average age was 28.6 years. Baseline CD4 cell count was 396 cel/mm3. A 7.7% were admitted with advanced pregnancy and 4.6% had a history of drug addiction. None of these variables had significant differences between both groups. The variables of gestational age at admission (15 vs. 21; P < 0.001), gestational age at the beginning of therapy (18 vs. 21; P < 0.001), CDC stage and baseline viral load (9750 vs. 644 copies/mL;P < 0.001) were statistically significant between Chileans and foreigners. 58% of the patients achieved undetectability at the time of delivery without differences between both groups. (55% vs. 63%; p0.42) Almost 90% of women with detectable viral load at delivery was less than 1000 copies/mL (88,9%). 93% received full vertical transmission protocol and the prematurity rate was 16.6%. The vertical transmission was 2.6% without differences between nationals and foreigners. In the postpartum follow-up,70% were retained, 73% of them undetectable on the latest follow-up visit. Conclusion Despite the cultural and language limitations, foreign patients maintained a compliance similar to those of Chile, achieving a low transmission rate vertical and good adherence to postpartum controls. Disclosures All authors: No reported disclosures.

Conformational changes in proteins are essential to their biological functions, from allosteric regulation to signal propagation. However, the transient nature of the intermediates along transition pathways hampers their experimental detection, making the mechanisms underlying these processes highly elusive. Here, applying an innovative combination of Principal Component Analysis (PCA) of experimental ensembles and coarse-grained simulations [1], we dissect the essential motions orchestrating biological functions for the highly studied ion channel GLIC. This prokaryotic protein, which has been solved in different functional states along the gating cycle, is a prototype for the Pentameric Ligand-Gated Ion Channels (PLGICs) that mediate synaptic communication. We show how the Principal Components (PCs) of the GLIC ensemble decode the core motions common to all the current structures, providing mathematical reaction coordinates to cluster them and reveal clearly the interconnecting pathways. Modeling GLIC as an elastic network in a Langevin simulation, we generate smooth trajectories between end-points that visit spontaneously multiple intermediate states along the transition, providing a realistic description of the mechanism. Finally, by direct analysis of the correlated motions along the dominant PCs we unveil an elegant mechanism to propagate information from the binding site throughout the protein [2]. Our approach provides a powerful and general theoretical framework to study conformational changes and synthetize the rich structural information deposited currently in the Protein Data Bank.1.Orellana L., Yoluk O., Orozco M., Lindahl E. Revealing conformational transition pathways by analysis of structurally rich X-ray ensembles and coarse-grained simulations (2015) (submitted)2.Fenwick R.B.∗, Orellana L.∗, Esteban-Martin S., Orozco M., Salvatella X. Correlated motions are a fundamental property of beta-sheets. Nature Communications (2014); 5: 4070. http://dx.doi.org/10.1038/ncomms5070 ∗ Shared First Authorship

Principal Components from Ligand-Gated Ion Channel Structures Enable Ensemble Studies of Microsecond-Scale Transitions

La calidad de educación universitaria en el Perú se rige por el Consejo de Evaluación, Acreditación y Certificación de la Calidad de la Educación Superior Universitaria (CONEAU). La ficha de evaluación de la CONEAU, en la carrera de Medicina, cuenta con 98 estándares de calificación, de los cuales el N° 33 está relacionado al número de estudiantes por docentes en las teorías y prácticas de laboratorio o prácticas clínicas (1). Durante los últimos años, la cantidad de vacantes ofrecidas de esta carrera se encuentra en aumento. Por este motivo es preciso determinar dicha relación para evaluar la calidad del desarrollo de enseñanza que el estudiante de medicina de la Universidad Nacional Mayor de San Marcos (UNMSM) recibe, de acuerdo a este indicador (2)., The quality of university education in Peru is governed by the Board of Evaluation, Accreditation and Certification of Quality University Education (CONEAU). The assessment sheet CONEAU in the medical career, has 98 qualification standards, of which No. 33 is related to the number of students per teacher in the theories and practices of laboratory or clinical practice (1). In recent years, the number of vacancies offered this career is on the rise. It is therefore necessary to determine this relationship to assess the quality of development of teaching medical student at the National University of San Marcos (San Marcos) is, according to this indicator (2).

Elastic network models (ENMs) are coarse-grained descriptions of proteins as networks of coupled harmonic oscillators. However, despite their widespread application to study collective movements, there is still no consensus parametrization for the ENMs. When compared to molecular dynamics (MD) flexibility in solution, the ENMs tend to disperse the important motions into multiple modes. We present here a new ENM, trained against a database of atomistic MD trajectories. The role of residue connectivity, the analytical form of the force constants, and the threshold for interactions were systematically explored. We found that contacts between the three nearest sequence neighbors are crucial determinants of the fundamental motions. We developed a new general potential function including both the sequential and spatial relationships between interacting residue pairs which is robust against size and fold variations. The proposed model provides a systematic improvement compared to standard ENMs: Not only do its results match the MD results-even for long time scales-but also the model is able to capture large X-ray conformational transitions as well as NMR ensemble diversity.

Sr. Editor: La cardiomiopatia de Tako-Tsubo (CT) fue descrita por Sato et al, en 1990, y reportada por primera vez en Japon, tambien llamada “sindrome de disfuncion transitoria del ventriculo izquierdo” ya que produce una disfuncion severa pero reversible y con buen pronostico para el paciente (1). Este sindrome afecta generalmente a mujeres de 50 a 80 anos, con pocos factores de riesgo cardiovascular, y habitualmente esta desencadenada por estres emocional y/o fisico debido al aumento de catecolaminas (2,3). La CT tiene una presentacion clinica similar al sindrome de infarto agudo del miocardio (SICA), por lo tanto su diagnostico es de suma importancia ya que representa el 1,7% al 2,2% de todos los casos diagnosticados como SICA (1,4) En el diagnostico de CT se proponen cuatro criterios modificados por la Clinica Mayo, basados en la presentacion clinica del paciente: 1) La discinesia o acinesia transitoria de los segmentos apicales y medios del ventriculo izquierdo, con distribucion vascular correspondiente a mas de una arteria epicardica; 2) La ausencia de enfermedad coronaria obstructiva o evidencia de rotura aguda de placa en la angiografia; 3) La nueva aparicion de anomalias en el trazado ECG, como elevacion del segmento ST o inversion de la onda T; 4) Ausencia de traumatismo craneoencefalico reciente o hemorragia subaracnoidea, feocromocitoma, miocarditis, miocardiopatia hipertrofica o “aturdimiento miocardico de origen isquemico” (5). Leer mas...

El año pasado se aprobó la Ley N° 30220 que establece parámetros para mejorar la educación superior universitaria. Ella ha generado preocupación en la plana docente y estudiantes de medicina de nuestra Facultad. Al analizar el capítulo VIII de dicha ley que manifiesta las facultades del Docente, el artículo 84 señala que la edad máxima para ejercer docencia en una universidad pública es setenta años. Aquellos que superen este límite de edad solo podrán ejercer la docencia como docentes extraordinarios. Además, les impide el ejercicio de algún cargo administrativo (1). Y los docentes extraordinarios (eméritos, honorarios y similares) no podrán superar el 10% del número total de docentes de la cátedra en el respectivo semestre., Last year Act No. 30220 which establishes parameters to improve university education was approved. She has raised concerns in the educational and medical students of our Faculty flat. When analyzing Chapter VIII of the Act which states the powers of Teachers, Article 84 states that the maximum age to practice teaching in a public university is seventy. Those who exceed this age limit may only exercise the extraordinary teaching and teachers. It also prevents them from exercising any administrative office (1). And the extraordinary teachers (emeritus, fees and the like) may not exceed 10% of the total number of teachers of the chair in the respective semester.

Epidermal Growth Factor Receptor (EGFR) signalling is supposed to be triggered by a ligand-induced conformational change of the extracellular domain from a closed, self-inhibited tethered monomer, to an open untethered state with a free dimerization arm. The ectodomain also untethers spontaneously, but the molecular mechanism is still unknown. Experiments with the mAb806 antibody have suggested the existence of a third untethered state, still uncharacterised, appearing transiently during the tethered to untethered transition, and which exposes a cryptic epitope hidden in the known conformers. Here, simulations of two ectodomain mutants (R84K and G39R) targeting a domain I-II hinge reveal a new untethered but compact conformation, which originates from a back-rotation of domain I exposing the mAb806 epitope as the EGFRvIII deletion does. The present findings point to different molecular processes for ligand-dependent and spontaneous untethering, and suggest that point mutations and the EGFRvIII deletion may share a common activation mechanism related to domain I positioning.

We present a new method for estimating pathways for conformational transitions in macromolecules from the use of discrete molecular dynamics and biasing techniques based on a combination of essential dynamics and Maxwell-Demon sampling techniques. The method can work with high efficiency at different levels of resolution, including the atomistic one, and can help to define initial pathways for further exploration by means of more accurate atomistic molecular dynamics simulations. The method is implemented in a freely available Web-based application accessible at http://mmb.irbbarcelona.org/MDdMD .

Flexibility is the key magnitude to understand the variety of functions of proteins. Unfortunately, its experimental study is quite difficult, and in fact, most experimental procedures are designed to reduce flexibility and allow a better definition of the structure. Theoretical approaches have become then the alternative but face serious timescale problems, since many biologically relevant deformation movements happen in a timescale that is far beyond the possibility of current atomistic models. In this complex scenario, coarse-grained simulation methods have emerged as a powerful and inexpensive alternative. Along this chapter, we will review these coarse-grained methods, and explain their physical foundations and their range of applicability.

Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance.To determine the most common mutations associated to anti-retroviral drug resistance in Chile.Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85% males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A).Mean CD4(+) cell count and viral load were 154 cells/microl and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 %, 62% and 22%, respectively. The most common mutations found were T215Y (46%), L10F (44%), Ml84V (3896), K103N (35%) and M41L (32%). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47% to NNRTI, 7% to NRTI, 4% to PI and 0.7% to all groups. During the four years of the study, there was a significant increase in NNRTI resistance.These data provides important information about the epidemiology of drug resistance mutations and should help to design new HAART strategies.

Background: Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance. Aim: To determine the most common mutations associated to anti-retroviral drug resistance in Chile. Materials and Methods: Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85% males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A). Results: Mean CD4+ cell count and viral load were 154 cells/fil and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 %, 62% and 22%, respectively. The most common mutations found were T215Y (46%), L10F (44%), Ml84V (3896), K103N (35%) and M41L (32%). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47% to NNRTI, 7% to NRTI, 4% to PI and 0.7% to all groups. During the four years of the study, there was a significant increase in NNRTI resistance. Conclusions: These data provides important information about the epidemiology of drug resistance mutations and should help to design newHAARTstrategies

The epidermal growth factor receptor (EGFR) is both amplified and frequently mutated in glioblastoma. While downstream inhibition of EGFR signaling through small molecule tyrosine kinase inhibitors has shown little clinical efficacy in glioblastoma, monoclonal antibody targeting is proving to be a promising alternative. The monoclonal antibody 806 (mAb806) specifically binds the most common EGFR mutant, EGFRvIII, along with a subset of amplified wild type EGFR, but not EGFR expressed at normal levels. The selectivity of mAb806 is thought to be due to its targeting a tumor-specific epitope of EGFR which is only accessible as the receptor transitions between an inactive tethered conformation to an active ligand-bound dimer. Here we used molecular dynamics simulations coupled with in vitro assays in glioblastoma cells to characterize the transitional conformation of EGFR in mAb806 binding. Focusing on the mutations R108K and G63R, molecular dynamics simulation revealed a spontaneous untethering of EGFR to a compact conformation, which is characterized by a backwards rotation of domain I-II exposing both the dimerization arm and the mAb806-epitope. This configuration is structurally equivalent to EGFRvIII, suggesting that several glioblastoma mutations converge to remove domain I from the dimerization interface. Next, we evaluated the effect of these point mutations on the ability of mAb806 to bind glioblastoma cells in vitro. Using site-directed mutagenesis coupled with lentiviral-transduction, we expressed EGFR-R108K or EGFR-G63R in U87 glioblastoma cells. Investigating mAb806 binding by FACS, we show that mAb806 binds the mutant cells five times greater than control cells, validating our simulation predictions. Future studies will examine the effect of mAb806 in an in vivo tumor model. Significantly, as these point mutations have been found in several GBM patients, our results indicate the possibility of a broader patient spectrum for the use of ABT-806, a humanized version of mAb806 currently in phase I clinical trials.