3D Surface Modeling From Point Clouds

The goal of this thesis is to implement software for creating 3D models from point clouds. Point clouds are acquired with stereo cameras, monocular systems or laser scanners. The created 3D models are triangular models or NURBS (Non-Uniform Rational B-Splines) models. Triangular models are constructed from selected areas from the point clouds and resulted triangular models are translated into a set of quads. The quads are further translated into an estimated grid structure and used for NURBS surface approximation. Finally, we have a set of NURBS surfaces which represent the whole model. The problem wasn’t so easy to solve. The selected triangular surface reconstruction algorithm did not deal well with noise in point clouds. To handle this problem, a clustering method is introduced for simplificating the model and removing noise. As we had better results with the smaller point clouds produced by clustering, we used points in clusters to better estimate the grids for NURBS models. The overall results were good when the point cloud did not have much noise. The point clouds with small amount of error had good results as the triangular model was solid. NURBS surface reconstruction performed well on solid models.

Streptavidin - A Versatile Binding Protein for Solid-Phase Immunoassays

Streptavidin, a tetrameric protein secreted by Streptomyces avidinii, binds tightly to a small growth factor biotin. One of the numerous applications of this high-affinity system comprises the streptavidin-coated surfaces of bioanalytical assays which serve as universal binders for straightforward immobilization of any biotinylated molecule. Proteins can be immobilized with a lower risk of denaturation using streptavidin-biotin technology in contrast to direct passive adsorption. The purpose of this study was to characterize the properties and effects of streptavidin-coated binding surfaces on the performance of solid-phase immunoassays and to investigate the contributions of surface modifications. Various characterization tools and methods established in the study enabled the convenient monitoring and binding capacity determination of streptavidin-coated surfaces. The schematic modeling of the monolayer surface and the quantification of adsorbed streptavidin disclosed the possibilities and the limits of passive adsorption. The defined yield of 250 ng/cm² represented approximately 65 % coverage compared with a modelled complete monolayer, which is consistent with theoretical surface models. Modifications such as polymerization and chemical activation of streptavidin resulted in a close to 10-fold increase in the biotin-binding densities of the surface compared with the regular streptavidin coating. In addition, the stability of the surface against leaching was improved by chemical modification. The increased binding densities and capacities enabled wider high-end dynamic ranges in the solid-phase immunoassays, especially when using the fragments of the capture antibodies instead of intact antibodies for the binding of the antigen. The binding capacity of the streptavidin surface was not, by definition, predictive of the low-end performance of the immunoassays nor the assay sensitivity. Other features such as non-specific binding, variation and leaching turned out to be more relevant. The immunoassays that use a direct surface readout measurement of time-resolved fluorescence from a washed surface are dependent on the density of the labeled antibodies in a defined area on the surface. The binding surface was condensed into a spot by coating streptavidin in liquid droplets into special microtiter wells holding a small circular indentation at the bottom. The condensed binding area enabled a denser packing of the labeled antibodies on the surface. This resulted in a 5 - 6-fold increase in the signal-to-background ratios and an equivalent improvement in the detection limits of the solid-phase immunoassays. This work proved that the properties of the streptavidin-coated surfaces can be modified and that the defined properties of the streptavidin-based immunocapture surfaces contribute to the performance of heterogeneous immunoassays.

Modeling the transport phenomena within arterial wall: porous media approach

The transport of macromolecules, such as low-density lipoprotein (LDL), and their accumulation in the layers of the arterial wall play a critical role in the creation and development of atherosclerosis. Atherosclerosis is a disease of large arteries e.g., the aorta, coronary, carotid, and other proximal arteries that involves a distinctive accumulation of LDL and other lipid-bearing materials in the arterial wall. Over time, plaque hardens and narrows the arteries. The flow of oxygen-rich blood to organs and other parts of the body is reduced. This can lead to serious problems, including heart attack, stroke, or even death. It has been proven that the accumulation of macromolecules in the arterial wall depends not only on the ease with which materials enter the wall, but also on the hindrance to the passage of materials out of the wall posed by underlying layers. Therefore, attention was drawn to the fact that the wall structure of large arteries is different than other vessels which are disease-resistant. Atherosclerosis tends to be localized in regions of curvature and branching in arteries where fluid shear stress (shear rate) and other fluid mechanical characteristics deviate from their normal spatial and temporal distribution patterns in straight vessels. On the other hand, the smooth muscle cells (SMCs) residing in the media layer of the arterial wall respond to mechanical stimuli, such as shear stress. Shear stress may affect SMC proliferation and migration from the media layer to intima. This occurs in atherosclerosis and intimal hyperplasia. The study of blood flow and other body fluids and of heat transport through the arterial wall is one of the advanced applications of porous media in recent years. The arterial wall may be modeled in both macroscopic (as a continuous porous medium) and microscopic scales (as a heterogeneous porous medium). In the present study, the governing equations of mass, heat and momentum transport have been solved for different species and interstitial fluid within the arterial wall by means of computational fluid dynamics (CFD). Simulation models are based on the finite element (FE) and finite volume (FV) methods. The wall structure has been modeled by assuming the wall layers as porous media with different properties. In order to study the heat transport through human tissues, the simulations have been carried out for a non-homogeneous model of porous media. The tissue is composed of blood vessels, cells, and an interstitium. The interstitium consists of interstitial fluid and extracellular fibers. Numerical simulations are performed in a two-dimensional (2D) model to realize the effect of the shape and configuration of the discrete phase on the convective and conductive features of heat transfer, e.g. the interstitium of biological tissues. On the other hand, the governing equations of momentum and mass transport have been solved in the heterogeneous porous media model of the media layer, which has a major role in the transport and accumulation of solutes across the arterial wall. The transport of Adenosine 5´-triphosphate (ATP) is simulated across the media layer as a benchmark to observe how SMCs affect on the species mass transport. In addition, the transport of interstitial fluid has been simulated while the deformation of the media layer (due to high blood pressure) and its constituents such as SMCs are also involved in the model. In this context, the effect of pressure variation on shear stress is investigated over SMCs induced by the interstitial flow both in 2D and three-dimensional (3D) geometries for the media layer. The influence of hypertension (high pressure) on the transport of lowdensity lipoprotein (LDL) through deformable arterial wall layers is also studied. This is due to the pressure-driven convective flow across the arterial wall. The intima and media layers are assumed as homogeneous porous media. The results of the present study reveal that ATP concentration over the surface of SMCs and within the bulk of the media layer is significantly dependent on the distribution of cells. Moreover, the shear stress magnitude and distribution over the SMC surface are affected by transmural pressure and the deformation of the media layer of the aorta wall. This work reflects the fact that the second or even subsequent layers of SMCs may bear shear stresses of the same order of magnitude as the first layer does if cells are arranged in an arbitrary manner. This study has brought new insights into the simulation of the arterial wall, as the previous simplifications have been ignored. The configurations of SMCs used here with elliptic cross sections of SMCs closely resemble the physiological conditions of cells. Moreover, the deformation of SMCs with high transmural pressure which follows the media layer compaction has been studied for the first time. On the other hand, results demonstrate that LDL concentration through the intima and media layers changes significantly as wall layers compress with transmural pressure. It was also noticed that the fraction of leaky junctions across the endothelial cells and the area fraction of fenestral pores over the internal elastic lamina affect the LDL distribution dramatically through the thoracic aorta wall. The simulation techniques introduced in this work can also trigger new ideas for simulating porous media involved in any biomedical, biomechanical, chemical, and environmental engineering applications.

Application of Computational Fluid Dynamics in Modeling Blood Flow in Human Thoracic Aorta

The aim of this study was to simulate blood flow in thoracic human aorta and understand the role of flow dynamics in the initialization and localization of atherosclerotic plaque in human thoracic aorta. The blood flow dynamics in idealized and realistic models of human thoracic aorta were numerically simulated in three idealized and two realistic thoracic aorta models. The idealized models of thoracic aorta were reconstructed with measurements available from literature, and the realistic models of thoracic aorta were constructed by image processing Computed Tomographic (CT) images. The CT images were made available by South Karelia Central Hospital in Lappeenranta. The reconstruction of thoracic aorta consisted of operations, such as contrast adjustment, image segmentations, and 3D surface rendering. Additional design operations were performed to make the aorta model compatible for the numerical method based computer code. The image processing and design operations were performed with specialized medical image processing software. Pulsatile pressure and velocity boundary conditions were deployed as inlet boundary conditions. The blood flow was assumed homogeneous and incompressible. The blood was assumed to be a Newtonian fluid. The simulations with idealized models of thoracic aorta were carried out with Finite Element Method based computer code, while the simulations with realistic models of thoracic aorta were carried out with Finite Volume Method based computer code. Simulations were carried out for four cardiac cycles. The distribution of flow, pressure and Wall Shear Stress (WSS) observed during the fourth cardiac cycle were extensively analyzed. The aim of carrying out the simulations with idealized model was to get an estimate of flow dynamics in a realistic aorta model. The motive behind the choice of three aorta models with distinct features was to understand the dependence of flow dynamics on aorta anatomy. Highly disturbed and nonuniform distribution of velocity and WSS was observed in aortic arch, near brachiocephalic, left common artery, and left subclavian artery. On the other hand, the WSS profiles at the roots of branches show significant differences with geometry variation of aorta and branches. The comparison of instantaneous WSS profiles revealed that the model with straight branching arteries had relatively lower WSS compared to that in the aorta model with curved branches. In addition to this, significant differences were observed in the spatial and temporal profiles of WSS, flow, and pressure. The study with idealized model was extended to study blood flow in thoracic aorta under the effects of hypertension and hypotension. One of the idealized aorta models was modified along with the boundary conditions to mimic the thoracic aorta under the effects of hypertension and hypotension. The results of simulations with realistic models extracted from CT scans demonstrated more realistic flow dynamics than that in the idealized models. During systole, the velocity in ascending aorta was skewed towards the outer wall of aortic arch. The flow develops secondary flow patterns as it moves downstream towards aortic arch. Unlike idealized models, the distribution of flow was nonplanar and heavily guided by the artery anatomy. Flow cavitation was observed in the aorta model which was imaged giving longer branches. This could not be properly observed in the model with imaging containing a shorter length for aortic branches. The flow circulation was also observed in the inner wall of the aortic arch. However, during the diastole, the flow profiles were almost flat and regular due the acceleration of flow at the inlet. The flow profiles were weakly turbulent during the flow reversal. The complex flow patterns caused a non-uniform distribution of WSS. High WSS was distributed at the junction of branches and aortic arch. Low WSS was distributed at the proximal part of the junction, while intermedium WSS was distributed in the distal part of the junction. The pulsatile nature of the inflow caused oscillating WSS at the branch entry region and inner curvature of aortic arch. Based on the WSS distribution in the realistic model, one of the aorta models was altered to induce artificial atherosclerotic plaque at the branch entry region and inner curvature of aortic arch. Atherosclerotic plaque causing 50% blockage of lumen was introduced in brachiocephalic artery, common carotid artery, left subclavian artery, and aortic arch. The aim of this part of the study was first to study the effect of stenosis on flow and WSS distribution, understand the effect of shape of atherosclerotic plaque on flow and WSS distribution, and finally to investigate the effect of lumen blockage severity on flow and WSS distributions. The results revealed that the distribution of WSS is significantly affected by plaque with mere 50% stenosis. The asymmetric shape of stenosis causes higher WSS in branching arteries than in the cases with symmetric plaque. The flow dynamics within thoracic aorta models has been extensively studied and reported here. The effects of pressure and arterial anatomy on the flow dynamic were investigated. The distribution of complex flow and WSS is correlated with the localization of atherosclerosis. With the available results we can conclude that the thoracic aorta, with complex anatomy is the most vulnerable artery for the localization and development of atherosclerosis. The flow dynamics and arterial anatomy play a role in the localization of atherosclerosis. The patient specific image based models can be used to diagnose the locations in the aorta vulnerable to the development of arterial diseases such as atherosclerosis.

Validation of a 3D model for oxygen combustion in a circulating fluidized bed

In this thesis, a model called CFB3D is validated for oxygen combustion in circulating fluidized bed boiler. The first part of the work consists of literature review in which circulating fluidized bed and oxygen combustion technologies are studied. In addition, the modeling of circulating fluidized bed furnaces is discussed and currently available industrial scale three-dimensional furnace models are presented. The main features of CFB3D model are presented along with the theories and equations related to the model parameters used in this work. The second part of this work consists of the actual research and modeling work including measurements, model setup, and modeling results. The objectives of this thesis is to study how well CFB3D model works with oxygen combustion compared to air combustion in circulating fluidized bed boiler and what model parameters need to be adjusted when changing from air to oxygen combustion. The study is performed by modeling two air combustion cases and two oxygen combustion cases with comparable boiler loads. The cases are measured at Ciuden 30 MWth Flexi-Burn demonstration plant in April 2012. The modeled furnace temperatures match with the measurements as well in oxygen combustion cases as in air combustion cases but the modeled gas concentrations differ from the measurements clearly more in oxygen combustion cases. However, the same model parameters are optimal for both air and oxygen combustion cases. When the boiler load is changed, some combustion and heat transfer related model parameters need to be adjusted. To improve the accuracy of modeling results, better flow dynamics model should be developed in the CFB3D model. Additionally, more measurements are needed from the lower furnace to find the best model parameters for each case. The validation work needs to be continued in order to improve the modeling results and model predictability.

Prediction of 3D structure and ligand-binding properties : ABC transporters and flavodiiron proteins from Synechocystis sp. strain PCC 6803

Cyanobacteria are unicellular, non-nitrogen-fixing prokaryotes, which perform photosynthesis similarly as higher plants. The cyanobacterium Synechocystis sp. strain PCC 6803 is used as a model organism in photosynthesis research. My research described herein aims at understanding the function of the photosynthetic machinery and how it responds to changes in the environment. Detailed knowledge of the regulation of photosynthesis in cyanobacteria can be utilized for biotechnological purposes, for example in the harnessing of solar energy for biofuel production. In photosynthesis, iron participates in electron transfer. Here, we focused on iron transport in Synechocystis sp. strain PCC 6803 and particularly on the environmental regulation of the genes encoding the FutA2BC ferric iron transporter, which belongs to the ABC transporter family. A homology model built for the ATP-binding subunit FutC indicates that it has a functional ATPbinding site as well as conserved interactions with the channel-forming subunit FutB in the transporter complex. Polyamines are important for the cell proliferation, differentiation and apoptosis in prokaryotic and eukaryotic cells. In plants, polyamines have special roles in stress response and in plant survival. The polyamine metabolism in cyanobacteria in response to environmental stress is of interest in research on stress tolerance of higher plants. In this thesis, the potd gene encoding an polyamine transporter subunit from Synechocystis sp. strain PCC 6803 was characterized for the first time. A homology model built for PotD protein indicated that it has capability of binding polyamines, with the preference for spermidine. Furthermore, in order to investigate the structural features of the substrate specificity, polyamines were docked into the binding site. Spermidine was positioned very similarly in Synechocystis PotD as in the template structure and had most favorable interactions of the docked polyamines. Based on the homology model, experimental work was conducted, which confirmed the binding preference. Flavodiiron proteins (Flv) are enzymes, which protect the cell against toxicity of oxygen and/or nitric oxide by reduction. In this thesis, we present a novel type of photoprotection mechanism in cyanobacteria by the heterodimer of Flv2/Flv4. The constructed homology model of Flv2/Flv4 suggests a functional heterodimer capable of rapid electron transfer. The unknown protein sll0218, encoded by the flv2-flv4 operon, is assumed to facilitate the interaction of the Flv2/Flv4 heterodimer and energy transfer between the phycobilisome and PSII. Flv2/Flv4 provides an alternative electron transfer pathway and functions as an electron sink in PSII electron transfer.

Probabilistic contact preferences in protein-ligand and protein-protein complexes

Modeller för intermolekulär växelvärkan utnyttjas brett inom biologin. Analys av kontakter mellan proteiner och läkemedelsforskning representerar typiska tillämpningsområden för dylika modeller. En modell som beskriver sådana molekylära växelverkningar kan utformas med hjälp av biofysisk teori, vilket tenderar att resultera i ytterst tung beräkningsbörda även för enkla tillämpningar. Ett alternativt sätt att formulera modeller är att utnyttja stora databaser som innehåller strukturmätningar gjorda med hjälp av till exempel röntgendiffraktion. Då man använder sig av empiriska mätdata direkt, möjliggör en statistisk modell att osäkerheten och inexaktheten i datat tas till hänsyn på ett adekvat sätt, samtidigt som beräkningsbördan håller sig på en rimligare nivå jämfört med kvantmekaniska metoder som i princip borde ge de optimala resultaten. I avhandlingen utvecklades en 3D modell för numerisk undersökning av intermolekulär växelverkan baserad på Bayesiansk statistik. Modellens syfte är att åstadkomma prognoser för det hurdana eller vilka molekylstrukturer prefereras i en given kontext, d.v.s. är mer sannolika inom ramen för interaktion. Modellen testades i essentiella molekyläromgivningar - en liten molekyl vid sin bindningsplats hos ett protein och en gränsyta mellan proteinerna i ett komplex. De erhållna numeriska resultaten motsvarar väl experimentella resultat som tidigare rapporterats i litteraturen, exempelvis kvalitativa bindningsaffiniteter och kemisk kännedom av vissa aminosyrors rumsliga förmågor att utgöra bindningar. I avhandlingen gjordes ytterligare preliminära tester av den statistiska ansatsen för modellering av den centrala molekylära strukturella anpassningsbarheten. I praktiken är den utvecklade modellen ämnad som ett led i en mer omfattande analysmetod, så som en s.k. farmakofor modell. Molekyylivuorovaikutusten mallintamista hyödynnetään laajasti biologisten kysymysten tarkastelussa. Tyypillisiä esimerkkejä sovelluskohteista ovat proteiinien väliset kontaktit ja lääkesuunnittelu. Vuorovaikutuksia kuvaavan mallin lähtökohta voi olla molekyyleihin liittyvä teoria, jolloin soveltamiseen liittyvä laskenta saattaa olla erityisen raskasta, tai suuri havaintojoukko joka on saatu aikaan esimerkiksi mittaamalla rakenteita röntgendiffraktio menetelmällä. Tilastollinen malli mahdollistaa havaintoaineistossa olevan epätarkkuuden ja epävarmuuden huomioimisen, samalla pitäen laskennallisen kuorman pienempänä verrattuna periaatteessa parhaan tuloksen antavaan kvanttimekaaniseen mallinnukseen. Väitöstyössä kehitettiin bayesiläiseen tilastotieteeseen perustuva 3D malli molekyylien välisten vuorovaikutusten laskennalliseen tarkasteluun. Mallin tehtävä on tuottaa ennusteita sen suhteen, minkä tai millaisten molekyylirakenteiden väliset kompleksit ovat etusijalla, toisin sanoen todennäköisempiä, vuorovaikutustilanteessa. Työssä kehitetyn menetelmän toimivuutta testattiin käyttötarkoituksen suhteen olennaisissa molekyyliympäristöissä - pieni molekyyli sitoutumiskohdassaan proteiinissa sekä rajapinta kahden proteiinin välilllä proteiinikompleksissa. Saadut laskennalliset tulokset vastasivat hyvin vertailuun käytettyjä kirjallisuudesta saatuja kokeellisia tuloksia, kuten laadullisia sitoutumisaffiniteetteja, sekä kemiallista tietoa esimerkiksi tiettyjen aminohappojen avaruudellisesta sidoksenmuodostuksesta. Väitöstyössä myös alustavasti testattiin tilastollista lähestymistapaa tärkeän molekyylien rakenteellisen mukautuvuuden mallintamiseen. Käytännössä malli on tarkoitettu osaksi jotakin laajempaa analyysimenetelmää, kuten farmakoforimallia.

From protein structure to function with bioinformatics

It has long been known that amino acids are the building blocks for proteins and govern their folding into specific three-dimensional structures. However, the details of this process are still unknown and represent one of the main problems in structural bioinformatics, which is a highly active research area with the focus on the prediction of three-dimensional structure and its relationship to protein function. The protein structure prediction procedure encompasses several different steps from searches and analyses of sequences and structures, through sequence alignment to the creation of the structural model. Careful evaluation and analysis ultimately results in a hypothetical structure, which can be used to study biological phenomena in, for example, research at the molecular level, biotechnology and especially in drug discovery and development. In this thesis, the structures of five proteins were modeled with templatebased methods, which use proteins with known structures (templates) to model related or structurally similar proteins. The resulting models were an important asset for the interpretation and explanation of biological phenomena, such as amino acids and interaction networks that are essential for the function and/or ligand specificity of the studied proteins. The five proteins represent different case studies with their own challenges like varying template availability, which resulted in a different structure prediction process. This thesis presents the techniques and considerations, which should be taken into account in the modeling procedure to overcome limitations and produce a hypothetical and reliable three-dimensional structure. As each project shows, the reliability is highly dependent on the extensive incorporation of experimental data or known literature and, although experimental verification of in silico results is always desirable to increase the reliability, the presented projects show that also the experimental studies can greatly benefit from structural models. With the help of in silico studies, the experiments can be targeted and precisely designed, thereby saving both money and time. As the programs used in structural bioinformatics are constantly improved and the range of templates increases through structural genomics efforts, the mutual benefits between in silico and experimental studies become even more prominent. Hence, reliable models for protein three-dimensional structures achieved through careful planning and thoughtful executions are, and will continue to be, valuable and indispensable sources for structural information to be combined with functional data.

Pituusleikkureiden 3D-suunnittelun kehittäminen

Tämä diplomityö tehtiin Valmet Technologies Oy:n Järvenpään toimipisteelle. Työn tavoitteena oli tutkia miten pituusleikkureiden 3D-suunnittelua voidaan tehostaa hyödyntämällä uuden 3D-CAD -järjestelmän ominaisuuksia optimaalisesti. Työ koostuu teoriaosuudesta, haastattelututkimuksesta sekä käytännön osuudesta. Teoriaosuudessa perehdytään pituusleikkurin toimintaan ja rakenteeseen, 3D-suunnittelun teoriaan sekä CATIA-järjestelmään. Teoriaosuudessa etsitään myös uusia näkökulmia 3D-suunnitteluun. Haastattelututkimuksessa kartoitetaan nykyinen suunnitteluprosessi, suunnittelun kehitettäviä kohteita, sekä käytössä olevia suunnittelumenetelmiä, jotka ovat todettu toimiviksi. Haastattelututkimuksessa haastatellaan Valmet Technologies Oy:n Järvenpään toimipisteessä työskenteleviä pituusleikkureiden pääsuunnittelijoita sekä heidän esimiehiään. Lisäksi erillisten haastattelujen avulla kerätään kokemuksia CATIA V6 -ohjelmiston käytöstä sekä suunnitteluohjelmiston vaihtumisesta. Käytännön osuuden tavoitteena on arvioida pituusleikkurin parametroitujen mallirakenteiden siirtämiseen sekä korjauksiin kuluvia aikamääriä kyseisiin toimenpiteisiin tarvittavien resurssien määrittämiseksi. Käytännön osuudessa siirretään kaksi Valmet OptiWin Drum Compact -pituusleikkurin parametroitua osakokonaisuutta uuteen CAD-järjestelmään ja niille suoritetaan tarvittavat korjaustoimenpiteet Tutkimuksen tulosten perusteella yhteisen mallinnusmetodologian puuttuminen on merkittävin kehityskohde suunnittelun kehittämisessä. Lopuksi luotiin kehitysehdotukset sekä implementointisuunnitelma, joiden avulla pituusleikkureiden 3D-suunnittelua voidaan kehittää ja CATIA V6 -ohjelmisto voidaan ottaa käyttöön tehokkaasti.

Human Ezrin: Prediction of the 3D structure and interactions with mTOR

The protein Ezrin, is a member of the ERM family (Ezrin, Radixin and Moesin) that links the F-actin to the plasma membrane. The protein is made of three domains namely the FERM domain, a central α-helical domain and the CERMAD domain. The residues in Ezrin such as Ser66, Tyr145, Tyr353 and Tyr477 regulate the function of the protein through phosphorylation. The protein is found in two distinct conformations of active and dormant (inactive) state. The initial step during the conformation change is the breakage of intramolecular interaction in dormant Ezrin by phosphorylation of residue Thr567. The dormant structure of human Ezrin was predicted computationally since only partial active form structure was available. The validation analysis showed that 99.7% residues were positioned in favored, allowed and generously allowed regions of the Ramachandran plot. The Z-score of Ezrin was −7.36, G-factor was 0.1, and the QMEAN score of the model was 0.61 indicating a good model for human Ezrin. The comparison of the conformations of the activated and dormant Ezrin showed a major shift in the F2 lobe (residues 142-149 and 161-177) while changes in the conformation induced mobility shifts in lobe F3 (residues 261 to 267). The 3D positions of the phosphorylation sites Tyr145, Tyr353, Tyr477, Tyr482 and Thr567 were also located. Using targeted molecular dynamic simulation, the molecular movements during conformational change from active to dormant were visualized. The dormant Ezrin auto-inhibits itself by a head-to-tail interaction of the N-terminal and C-terminal residues. The trajectory shows the breakage of the interactions and mobility of the CERMAD domain away from the FERM domain. Protein docking and clustering analysis were used to predict the residues involved in the interaction between dormant Ezrin and mTOR. Residues Tyr477 and Tyr482 were found to be involved in interaction with mTOR.