A Molecular Dynamics Study Proposing the Existence of Structural Interaction Between Cancer Cell Receptor and RNA Aptamer

2020 ◽  
Vol 30 (11) ◽  
pp. 4520-4532
Author(s):  
Mohaddeseh Habibzadeh Mashatooki ◽  
Jaber Jahanbin Sardroodi
Keyword(s):  
Molecular Dynamics ◽  
Cancer Cell ◽  
Cell Receptor ◽  
Rna Aptamer ◽  
Structural Interaction

scholarly journals Quantitative real-time imaging of molecular dynamics during cancer cell invasion and metastasis in vivo

2009 ◽  
Vol 3 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Paul Timpson ◽  
Alan Serrels ◽  
Marta Canel ◽  
Margaret C. Frame ◽  
Valerie G. Brunton ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Real Time ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Real Time Imaging

Elucidation of chemosensitization effect of acridones in cancer cell lines: Combined pharmacophore modeling, 3D QSAR, and molecular dynamics studies

2018 ◽  
Vol 74 ◽  
pp. 63-75 ◽  
Author(s):  
Deepak Reddy Gade ◽  
Amareswararao Makkapati ◽  
Rajesh Babu Yarlagadda ◽  
Godefridus J. Peters ◽  
B.S. Sastry ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Lines ◽  
Cancer Cell ◽  
3D Qsar ◽  
Cancer Cell Lines ◽  
Pharmacophore Modeling

scholarly journals Structural variability and concerted motions of the T cell receptor – CD3 complex

2021 ◽  
Author(s):  
Prithvi R. Pandey ◽  
Bartosz Różycki ◽  
Reinhard Lipowsky ◽  
Thomas R. Weikl
Keyword(s):  
Molecular Dynamics ◽  
T Cell ◽  
Molecular Dynamics Simulations ◽  
T Cell Receptor ◽  
Tilt Angle ◽  
Structural Changes ◽  
Cell Receptor ◽  
Transmembrane Helices ◽  
Dynamics Simulations ◽  
Tcr Activation

AbstractWe investigate the structural and orientational variability of the membrane-embedded T cell receptor (TCR) – CD3 complex in extensive atomistic molecular dynamics simulations based on the recent cryo-EM structure determined by Dong et al. (2019). We find that the TCR extracellular (EC) domain is highly variable in its orientation by attaining tilt angles relative to the membrane normal that range from 15° to 55°. The tilt angle of the TCR EC domain is both coupled to a rotation of the domain and to characteristic changes throughout the TCR – CD3 complex, in particular in the EC interactions of the Cβ FG loop of the TCR, as well as in the orientation of transmembrane helices. The concerted motions of the membrane-embedded TCR – CD3 complex revealed in our simulations provide atomistic insights for force-based models of TCR activation, which involve such structural changes in response to tilt-inducing forces on antigen-bound TCRs.

scholarly journals Embelin inhibits TNF-α converting enzyme and cancer cell metastasis: molecular dynamics and experimental evidence

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaspreet Kaur Dhanjal ◽  
Nupur Nigam ◽  
Sudhanshu Sharma ◽  
Anupama Chaudhary ◽  
Sunil C Kaul ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Experimental Evidence ◽  
Cancer Cell ◽  
Converting Enzyme ◽  
Cell Metastasis ◽  
Tnf Α

scholarly journals 4094 Structural Determinants of Immunogenicity for Peptide-Based Immunotherapy

2020 ◽  
Vol 4 (s1) ◽  
pp. 16-16
Author(s):  
Jason Devlin ◽  
Jesus Alonso ◽  
Grant Keller ◽  
Sara Bobisse ◽  
Alexandre Harari ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
T Cell ◽  
Molecular Dynamics Simulations ◽  
Crystal Structures ◽  
T Cell Receptor ◽  
Tumor Regression ◽  
Recombinant Expression ◽  
Cell Receptor ◽  
Protein Crystal ◽  
Dynamics Simulations

OBJECTIVES/GOALS: Neoantigen vaccine immunotherapies have shown promise in clinical trials, but identifying which peptides to include in a vaccine remains a challenge. We aim to establish that molecular structural features can help predict which neoantigens to target to achieve tumor regression. METHODS/STUDY POPULATION: Proteins were prepared by recombinant expression in E. coli followed by in vitro refolding. Correctly folded proteins were purified by chromatography. Affinities of protein-protein interactions were measured by surface plasmon resonance (SPR) and thermal stabilities of proteins were determined by differential scanning fluorimetry. All experiments were performed at least in triplicate. Protein crystals were obtained by hanging drop vapor diffusion. The protein crystal structures were solved by molecular replacement and underwent several rounds of automated refinement. Molecular dynamics simulations were performed using the AMBER molecular dynamics package. RESULTS/ANTICIPATED RESULTS: A T cell receptor (TCR) expressed by tumor-infiltrating T cells exhibited a 20-fold stronger binding affinity to the neoantigen peptide compared to the self-peptide. X-ray crystal structures of the peptides with the major histocompatibility complex (MHC) protein demonstrated that a non-mutated residue in the peptide samples different positions with the mutation. The difference in conformations of the non-mutated residue was supported by molecular dynamics simulations. Crystal structures of the TCR engaging both peptide/MHCs suggested that the conformation favored by the mutant peptide was crucial for TCR binding. The TCR bound the neoantigen/MHC with faster binding kinetics. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that the mutation impacts the conformation of another residue in the peptide, and this alteration allows for more favorable T cell receptor binding to the neoantigen. This highlights the potential of non-mutated residues in contributing to neoantigen recognition.

scholarly journals Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy

2017 ◽  
Vol 4 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Kshitij Gupta ◽  
Anu Puri ◽  
Bruce A. Shapiro
Keyword(s):  
Cancer Cell ◽  
Viral Vectors ◽  
Sirna Delivery ◽  
Cell Receptor ◽  
Rna Molecules ◽  
Safety Issues ◽  
Non Coding Rna ◽  
Anionic Charge ◽  
Rapid Clearance ◽  
Target Effects

AbstractRNA interference (RNAi) has been regarded as a vital asset in the field of therapeutics as it has the capability to silence various disease causing genes including those that cause cancer. Small non-coding RNA molecules such as short interfering RNAs (siRNAs) are one of the extensively studied RNAi inducers for gene modulations. However, the delivery of RNAi inducers including siRNAs is compromised due to the barriers imposed by the biological system such as degradation by nucleases, rapid clearance, high anionic charge, immunogenicity and off-target effects. Viral vectors, in general exhibit high transfection efficiencies but are expensive and likely to confer immunological and safety issues. Therefore, non-viral cationic vectors (NVCVs) have received considerable attention to not only address these issues but also for developing efficacious siRNA delivery vectors. In this review, we will first discuss the historical development of various NVCVs and then will discuss functionalized NVCVs with linkers that provide stability, as well as respond to the cancer cell environment and with cancer cell receptor specific ligands to explicitly target them for improved siRNA efficacy. Multifunctional NVCVs (MNVCVs) that employ multiple synergistically working components to aid siRNA delivery efficacy are also discussed.

scholarly journals Targeting N-myristoylation for therapy of B-cell lymphomas

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Erwan Beauchamp ◽  
Megan C. Yap ◽  
Aishwarya Iyer ◽  
Maneka A. Perinpanayagam ◽  
Jay M. Gamma ◽  
...  
Keyword(s):  
B Cell ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cell Receptor ◽  
B Cell Lymphomas ◽  
Cancer Cell Death ◽  
Anti Cancer ◽  
Xenograft Models ◽  
Patients Experience

Abstract Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often have increased N-myristoyltransferase (NMT) expression, NMTs were proposed as anti-cancer targets. To systematically investigate this, we performed robotic cancer cell line screens and discovered a marked sensitivity of hematological cancer cell lines, including B-cell lymphomas, to the potent pan-NMT inhibitor PCLX-001. PCLX-001 treatment impacts the global myristoylation of lymphoma cell proteins and inhibits early B-cell receptor (BCR) signaling events critical for survival. In addition to abrogating myristoylation of Src family kinases, PCLX-001 also promotes their degradation and, unexpectedly, that of numerous non-myristoylated BCR effectors including c-Myc, NFκB and P-ERK, leading to cancer cell death in vitro and in xenograft models. Because some treated lymphoma patients experience relapse and die, targeting B-cell lymphomas with a NMT inhibitor potentially provides an additional much needed treatment option for lymphoma.

scholarly journals Elucidating the T Cell Receptor Transmembrane Organization via Multi-Scale Molecular Dynamics Simulations

2015 ◽  
Vol 108 (2) ◽  
pp. 558a-559a
Author(s):  
Antreas C. Kalli ◽  
Andre Cohnen ◽  
Oreste Acuto ◽  
Mark S.P. Sansom
Keyword(s):  
Molecular Dynamics ◽  
T Cell ◽  
Molecular Dynamics Simulations ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Multi Scale ◽  
Dynamics Simulations

scholarly journals The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor

2020 ◽  
Author(s):  
Esther S. Brielle ◽  
Dina Schneidman-Duhovny ◽  
Michal Linial
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Cell Receptor ◽  
Host Recognition ◽  
Interface Residue ◽  
Binding Affinities ◽  
Temporal Dimension ◽  
Binding Interface ◽  
Residue Contacts ◽  
Dynamics Simulations

AbstractThe COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies.One Sentence SummaryMolecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.

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