Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways

Asif Mir; Syeda Naqsh e Zahra; Sobiah Rauf

doi:doi:10.11648/j.ijcocr.20160101.12

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Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways

Asif Mir, Syeda Naqsh e Zahra, Sobiah Rauf

Published in International Journal of Clinical Oncology and Cancer Research (Volume 1, Issue 1)

Received: 15 October 2016 Accepted: 3 December 2016 Published: 9 January 2017

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Abstract

The fundamentals of structure-based drug designing rely on protein-ligand interactions, which play a significant role to open a gateway from identification of active residues and development of potential drugs. The endeavor behind this work is to select most susceptible genes p53 and AKT1 which plays a vital role in lung cancer pathogencity. In a queue to deliberate the crucial role of these genes in-silico experimental strategy was adopted. 3-D structure of p53 generated by YASARA showed 50.9% sequence identity with 2PCX-A and Z-score of -0.276 while AKT1 showed 66.3% sequence identity with 3QKL-A and Z-score of 0.036. Mutational analysis revealed that R273L and C275Y mutations of p53 destabilize the DNA binding domain, while E17K mutation of AKT1directly affect the binding of the ligand as this residues lines the pocket. Molecular docking was performed using ligands Staurosporine and Nutlin-3 retrieved form ZINC database. Blind docking experiment revealed that p53 involve non polar (Leu206, Leu188, Pro190), acidic (Glu204, Tyr 205) and basic (Arg202) as most interacting residues. AKT1 interactions with ligand Staurosporine revealed nonpolar (Val164, Phe438, Phe442, Phe 236, Phe 237, Phe 161), polar (Gly159, Gly157, Gly234, Gly 278), basic (Lys163, Lys158, Lys 276, Lys 179), acidic (Asp439, Glu278) as most interacting residues. It is assumed that current study will play a significant contribution to design potential drug inhibitors by utilizing most interactive residue information with Nutlin-3 and Staurosporine ligands to restrain the interaction between p53 pathways and epidermal growth pathways. Structural based receptor-ligand interactions likely to be used against anti-cancer therapy.

Published in	International Journal of Clinical Oncology and Cancer Research (Volume 1, Issue 1)
DOI	10.11648/j.ijcocr.20160101.12
Page(s)	6-14
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

P53, AKT1, Lung Cancer, Comparative Modeling, Molecular Docking, Mutational Analysis

References

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APA Style

Asif Mir, Syeda Naqsh e Zahra, Sobiah Rauf. (2017). Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. International Journal of Clinical Oncology and Cancer Research, 1(1), 6-14. https://doi.org/10.11648/j.ijcocr.20160101.12

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ACS Style

Asif Mir; Syeda Naqsh e Zahra; Sobiah Rauf. Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. Int. J. Clin. Oncol. Cancer Res. 2017, 1(1), 6-14. doi: 10.11648/j.ijcocr.20160101.12

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AMA Style

Asif Mir, Syeda Naqsh e Zahra, Sobiah Rauf. Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. Int J Clin Oncol Cancer Res. 2017;1(1):6-14. doi: 10.11648/j.ijcocr.20160101.12

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@article{10.11648/j.ijcocr.20160101.12,
  author = {Asif Mir and Syeda Naqsh e Zahra and Sobiah Rauf},
  title = {Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {1},
  number = {1},
  pages = {6-14},
  doi = {10.11648/j.ijcocr.20160101.12},
  url = {https://doi.org/10.11648/j.ijcocr.20160101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20160101.12},
  abstract = {The fundamentals of structure-based drug designing rely on protein-ligand interactions, which play a significant role to open a gateway from identification of active residues and development of potential drugs. The endeavor behind this work is to select most susceptible genes p53 and AKT1 which plays a vital role in lung cancer pathogencity. In a queue to deliberate the crucial role of these genes in-silico experimental strategy was adopted. 3-D structure of p53 generated by YASARA showed 50.9% sequence identity with 2PCX-A and Z-score of -0.276 while AKT1 showed 66.3% sequence identity with 3QKL-A and Z-score of 0.036. Mutational analysis revealed that R273L and C275Y mutations of p53 destabilize the DNA binding domain, while E17K mutation of AKT1directly affect the binding of the ligand as this residues lines the pocket. Molecular docking was performed using ligands Staurosporine and Nutlin-3 retrieved form ZINC database. Blind docking experiment revealed that p53 involve non polar (Leu206, Leu188, Pro190), acidic (Glu204, Tyr 205) and basic (Arg202) as most interacting residues. AKT1 interactions with ligand Staurosporine revealed nonpolar (Val164, Phe438, Phe442, Phe 236, Phe 237, Phe 161), polar (Gly159, Gly157, Gly234, Gly 278), basic (Lys163, Lys158, Lys 276, Lys 179), acidic (Asp439, Glu278) as most interacting residues. It is assumed that current study will play a significant contribution to design potential drug inhibitors by utilizing most interactive residue information with Nutlin-3 and Staurosporine ligands to restrain the interaction between p53 pathways and epidermal growth pathways. Structural based receptor-ligand interactions likely to be used against anti-cancer therapy.},
 year = {2017}
}

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TY  - JOUR
T1  - Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways
AU  - Asif Mir
AU  - Syeda Naqsh e Zahra
AU  - Sobiah Rauf
Y1  - 2017/01/09
PY  - 2017
N1  - https://doi.org/10.11648/j.ijcocr.20160101.12
DO  - 10.11648/j.ijcocr.20160101.12
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 6
EP  - 14
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20160101.12
AB  - The fundamentals of structure-based drug designing rely on protein-ligand interactions, which play a significant role to open a gateway from identification of active residues and development of potential drugs. The endeavor behind this work is to select most susceptible genes p53 and AKT1 which plays a vital role in lung cancer pathogencity. In a queue to deliberate the crucial role of these genes in-silico experimental strategy was adopted. 3-D structure of p53 generated by YASARA showed 50.9% sequence identity with 2PCX-A and Z-score of -0.276 while AKT1 showed 66.3% sequence identity with 3QKL-A and Z-score of 0.036. Mutational analysis revealed that R273L and C275Y mutations of p53 destabilize the DNA binding domain, while E17K mutation of AKT1directly affect the binding of the ligand as this residues lines the pocket. Molecular docking was performed using ligands Staurosporine and Nutlin-3 retrieved form ZINC database. Blind docking experiment revealed that p53 involve non polar (Leu206, Leu188, Pro190), acidic (Glu204, Tyr 205) and basic (Arg202) as most interacting residues. AKT1 interactions with ligand Staurosporine revealed nonpolar (Val164, Phe438, Phe442, Phe 236, Phe 237, Phe 161), polar (Gly159, Gly157, Gly234, Gly 278), basic (Lys163, Lys158, Lys 276, Lys 179), acidic (Asp439, Glu278) as most interacting residues. It is assumed that current study will play a significant contribution to design potential drug inhibitors by utilizing most interactive residue information with Nutlin-3 and Staurosporine ligands to restrain the interaction between p53 pathways and epidermal growth pathways. Structural based receptor-ligand interactions likely to be used against anti-cancer therapy.
VL  - 1
IS  - 1
ER  -

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Author Information

Asif Mir

Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan
Syeda Naqsh e Zahra

Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan
Sobiah Rauf

Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan

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APA Style

Asif Mir, Syeda Naqsh e Zahra, Sobiah Rauf. (2017). Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. International Journal of Clinical Oncology and Cancer Research, 1(1), 6-14. https://doi.org/10.11648/j.ijcocr.20160101.12

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ACS Style

Asif Mir; Syeda Naqsh e Zahra; Sobiah Rauf. Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. Int. J. Clin. Oncol. Cancer Res. 2017, 1(1), 6-14. doi: 10.11648/j.ijcocr.20160101.12

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AMA Style

Asif Mir, Syeda Naqsh e Zahra, Sobiah Rauf. Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways. Int J Clin Oncol Cancer Res. 2017;1(1):6-14. doi: 10.11648/j.ijcocr.20160101.12

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@article{10.11648/j.ijcocr.20160101.12,
  author = {Asif Mir and Syeda Naqsh e Zahra and Sobiah Rauf},
  title = {Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways},
  journal = {International Journal of Clinical Oncology and Cancer Research},
  volume = {1},
  number = {1},
  pages = {6-14},
  doi = {10.11648/j.ijcocr.20160101.12},
  url = {https://doi.org/10.11648/j.ijcocr.20160101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcocr.20160101.12},
  abstract = {The fundamentals of structure-based drug designing rely on protein-ligand interactions, which play a significant role to open a gateway from identification of active residues and development of potential drugs. The endeavor behind this work is to select most susceptible genes p53 and AKT1 which plays a vital role in lung cancer pathogencity. In a queue to deliberate the crucial role of these genes in-silico experimental strategy was adopted. 3-D structure of p53 generated by YASARA showed 50.9% sequence identity with 2PCX-A and Z-score of -0.276 while AKT1 showed 66.3% sequence identity with 3QKL-A and Z-score of 0.036. Mutational analysis revealed that R273L and C275Y mutations of p53 destabilize the DNA binding domain, while E17K mutation of AKT1directly affect the binding of the ligand as this residues lines the pocket. Molecular docking was performed using ligands Staurosporine and Nutlin-3 retrieved form ZINC database. Blind docking experiment revealed that p53 involve non polar (Leu206, Leu188, Pro190), acidic (Glu204, Tyr 205) and basic (Arg202) as most interacting residues. AKT1 interactions with ligand Staurosporine revealed nonpolar (Val164, Phe438, Phe442, Phe 236, Phe 237, Phe 161), polar (Gly159, Gly157, Gly234, Gly 278), basic (Lys163, Lys158, Lys 276, Lys 179), acidic (Asp439, Glu278) as most interacting residues. It is assumed that current study will play a significant contribution to design potential drug inhibitors by utilizing most interactive residue information with Nutlin-3 and Staurosporine ligands to restrain the interaction between p53 pathways and epidermal growth pathways. Structural based receptor-ligand interactions likely to be used against anti-cancer therapy.},
 year = {2017}
}

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TY  - JOUR
T1  - Comparative Modeling and Molecular Docking Study of P53 and AKT1, Genes of Lung Cancer Pathways
AU  - Asif Mir
AU  - Syeda Naqsh e Zahra
AU  - Sobiah Rauf
Y1  - 2017/01/09
PY  - 2017
N1  - https://doi.org/10.11648/j.ijcocr.20160101.12
DO  - 10.11648/j.ijcocr.20160101.12
T2  - International Journal of Clinical Oncology and Cancer Research
JF  - International Journal of Clinical Oncology and Cancer Research
JO  - International Journal of Clinical Oncology and Cancer Research
SP  - 6
EP  - 14
PB  - Science Publishing Group
SN  - 2578-9511
UR  - https://doi.org/10.11648/j.ijcocr.20160101.12
AB  - The fundamentals of structure-based drug designing rely on protein-ligand interactions, which play a significant role to open a gateway from identification of active residues and development of potential drugs. The endeavor behind this work is to select most susceptible genes p53 and AKT1 which plays a vital role in lung cancer pathogencity. In a queue to deliberate the crucial role of these genes in-silico experimental strategy was adopted. 3-D structure of p53 generated by YASARA showed 50.9% sequence identity with 2PCX-A and Z-score of -0.276 while AKT1 showed 66.3% sequence identity with 3QKL-A and Z-score of 0.036. Mutational analysis revealed that R273L and C275Y mutations of p53 destabilize the DNA binding domain, while E17K mutation of AKT1directly affect the binding of the ligand as this residues lines the pocket. Molecular docking was performed using ligands Staurosporine and Nutlin-3 retrieved form ZINC database. Blind docking experiment revealed that p53 involve non polar (Leu206, Leu188, Pro190), acidic (Glu204, Tyr 205) and basic (Arg202) as most interacting residues. AKT1 interactions with ligand Staurosporine revealed nonpolar (Val164, Phe438, Phe442, Phe 236, Phe 237, Phe 161), polar (Gly159, Gly157, Gly234, Gly 278), basic (Lys163, Lys158, Lys 276, Lys 179), acidic (Asp439, Glu278) as most interacting residues. It is assumed that current study will play a significant contribution to design potential drug inhibitors by utilizing most interactive residue information with Nutlin-3 and Staurosporine ligands to restrain the interaction between p53 pathways and epidermal growth pathways. Structural based receptor-ligand interactions likely to be used against anti-cancer therapy.
VL  - 1
IS  - 1
ER  -

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