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    Directed Evolution of the Asparaginase Enzyme to Alter Substrate Specificity

    , M.Sc. Thesis Sharif University of Technology Yousefi, Danial (Author) ; Kalhor, Hamid Reza (Supervisor)
    Abstract
    Asparagainase is a therapeutic enzyme which has been a subject of research for decades. The enzyme catalyzes the hydrolysis of the amide group in asparagine and similar amides. Altering the substrate specificity and stabilization of this enzyme can increase its therapeutic properties. Moreover, asparaginases may be evolved to catalyze the hydrolysis of other similar compounds. These can be achieved through directed evolution and computational methods.In this study, the gene encoding L-asparaginase II enzyme from E. coli was amplified by polymerase chain reaction (PCR) and was cloned into an expression vector. The recombinant protein was expressed by an appropriate host secreting the... 

    Graphene-based nanoparticles as potential treatment options for parkinson’s disease: A molecular dynamics study

    , Article International Journal of Nanomedicine ; Volume 15 , 2020 , Pages 6887-6903 Alimohammadi, E ; Khedri, M ; Jahromi, A. M ; Maleki, R ; Rezaian, M ; Sharif University of Technology
    Dove Medical Press Ltd  2020
    Abstract
    Introduction: The study of abnormal aggregation of proteins in different tissues of the body has recently earned great attention from researchers in various fields of science. Concerning neurological diseases, for instance, the accumulation of amyloid fibrils can contribute to Parkinson’s disease, a progressively severe neurodegenerative disorder. The most prominent features of this disease are the degeneration of neurons in the substantia nigra and accumulation of α-synuclein aggregates, especially in the brainstem, spinal cord, and cortical areas. Dopamine replacement therapies and other medications have reduced motor impairment and had positive consequences on patients’ quality of life.... 

    Evolution of 'ligand-deffusion chreodes' on protein-surface models: A genetic-algorithm study

    , Article Chemistry and Biodiversity ; Volume 4, Issue 12 , 2007 , Pages 2766-2771 ; 16121872 (ISSN) Marashi, A ; Kargar, M ; Katanforoush, A ; Abolhassani, H ; Sadeghi, M ; Sharif University of Technology
    2007
    Abstract
    Lattice models have been previously used to model ligand diffusion on protein surfaces. Using such models, it has been shown that the presence of pathways (or 'chreodes') of consecutive residues with certain properties can decrease the number of steps required for the arrival of a ligand at the active site. In this work, we show that, based on a genetic algorithm, ligand-diffusion pathways can evolve on a protein surface, when this surface is selected for shortening the travel length toward the active site. Biological implications of these results are discussed. © 2007 Verlag Helvetica Chimica Acta AG, Zürich  

    Dynamics of antimicrobial peptide encapsulation in carbon nanotubes: the role of hydroxylation

    , Article International Journal of Nanomedicine ; Volume 17 , 2022 , Pages 125-136 ; 11769114 (ISSN) Dehaghani, M.Z ; Yousefi, F ; Seidi, F ; Sajadi, S. M ; Rabiee, N ; Habibzadeh, S ; Esmaeili, A ; Mashhadzadeh, A. H ; Spitas, C ; Mostafavi, E ; Saeb, M. R ; Sharif University of Technology
    Dove Medical Press Ltd  2022
    Abstract
    Introduction: Carbon nanotubes (CNTs) have been widely employed as biomolecule carriers, but there is a need for further functionalization to broaden their therapeutic application in aqueous environments. A few reports have unraveled biomolecule–CNT interactions as a measure of response of the nanocarrier to drug-encapsulation dynamics. Methods: Herein, the dynamics of encapsulation of the antimicrobial peptide HA-FD-13 (accession code 2L24) into CNTs and hydroxylated CNTs (HCNTs) is discussed. Results: The van der Waals (vdW) interaction energy of CNT–peptide and HCNT–peptide complexes decreased, reaching −110.6 and −176.8 kcal.Mol−1, respectively, once encapsulation of the peptide inside... 

    Structural stability and sustained release of protein from a multilayer nanofiber/nanoparticle composite

    , Article International Journal of Biological Macromolecules ; Volume 75 , April , 2015 , Pages 248-257 ; 01418130 (ISSN) Vakilian, S ; Mashayekhan, S ; Shabani, I ; Khorashadizadeh, M ; Fallah, A ; Soleimani, M ; Sharif University of Technology
    Elsevier  2015
    Abstract
    The cellular microenvironment can be engineered through the utilization of various nano-patterns and matrix-loaded bioactive molecules. In this study, a multilayer system of electrospun scaffold containing chitosan nanoparticles was introduced to overcome the common problems of instability and burst release of proteins from nanofibrous scaffolds. Bovine serum albumin (BSA)-loaded chitosan nanoparticles was fabricated based on ionic gelation interaction between chitosan and sodium tripolyphosphate. Suspension electrospinning was employed to fabricate poly-e{open}-caprolacton (PCL) containing protein-loaded chitosan nanoparticles with a core-shell structure. To obtain the desired scaffold... 

    Efficient protein immobilization on polyethersolfone electrospun nanofibrous membrane via covalent binding for biosensing applications

    , Article Materials Science and Engineering C ; Volume 58 , 2016 , Pages 586-594 ; 09284931 (ISSN) Mahmoudifard, M ; Soudi, S ; Soleimani, M ; Hosseinzadeh, S ; Esmaeili, E ; Vossoughi, M ; Sharif University of Technology
    Elsevier Ltd  2016
    Abstract
    In this paper we introduce novel strategy for antibody immobilization using high surface area electrospun nanofibrous membrane based on ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling chemistry. To present the high performance of proposed biosensors, anti-staphylococcus enterotoxin B (anti-SEB) was used as a model to demonstrate the utility of our proposed system. Polymer solution of polyethersolfone was used to fabricate fine nanofibrous membrane. Moreover, industrial polyvinylidene fluoride membrane and conventional microtiter plate were also used to compare the efficiency of antibody immobilization. Scanning electron microscopy images were taken to...