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Simulation of different truncated p16(INK4a) forms and in silico study of interaction with Cdk4.

Fahham N, Ghahremani MH, Sardari S, Vaziri B, Ostad SN - Cancer Inform (2008)

Bottom Line: Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms.The free energies were compatible with that of p16 full length original form, the full length.It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute, Tehran, Iran.

ABSTRACT
Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G(1)-S phase restriction point and p16(INK4a), a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

No MeSH data available.


Related in: MedlinePlus

Different 3D truncated structures generated by homology modeling. A) 44 amino acids deletion of C-terminal; B) 76 amino acids deletion of C-terminal; C) 47 amino acids of N-terminal; D) amino acids 42–103; E) amino acids 66–114; F) 41 amino acids deletion of N-terminal G) 65 amino acids deletion of N-terminal H) 79 amino acids deletion of N-terminal.
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f3-cin-07-01: Different 3D truncated structures generated by homology modeling. A) 44 amino acids deletion of C-terminal; B) 76 amino acids deletion of C-terminal; C) 47 amino acids of N-terminal; D) amino acids 42–103; E) amino acids 66–114; F) 41 amino acids deletion of N-terminal G) 65 amino acids deletion of N-terminal H) 79 amino acids deletion of N-terminal.

Mentions: Structures were generated by homology modeling. Three models were generated in pdb format in each case, of which the final model was selected considering the lowest free energy (kcal/mol). The Ramachandran plots provided by the GENO3D full model analysis reported that 98.9%, 98.4%, 94.6%, 98%, 100%, 97.9%, 100%, 98.4% of the residues fell within the allowed regions according to truncated structures: A, B, C, D, E, F, G and H respectively. Figure 3 shows the tertiary structures generated by homology modeling.


Simulation of different truncated p16(INK4a) forms and in silico study of interaction with Cdk4.

Fahham N, Ghahremani MH, Sardari S, Vaziri B, Ostad SN - Cancer Inform (2008)

Different 3D truncated structures generated by homology modeling. A) 44 amino acids deletion of C-terminal; B) 76 amino acids deletion of C-terminal; C) 47 amino acids of N-terminal; D) amino acids 42–103; E) amino acids 66–114; F) 41 amino acids deletion of N-terminal G) 65 amino acids deletion of N-terminal H) 79 amino acids deletion of N-terminal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2664699&req=5

f3-cin-07-01: Different 3D truncated structures generated by homology modeling. A) 44 amino acids deletion of C-terminal; B) 76 amino acids deletion of C-terminal; C) 47 amino acids of N-terminal; D) amino acids 42–103; E) amino acids 66–114; F) 41 amino acids deletion of N-terminal G) 65 amino acids deletion of N-terminal H) 79 amino acids deletion of N-terminal.
Mentions: Structures were generated by homology modeling. Three models were generated in pdb format in each case, of which the final model was selected considering the lowest free energy (kcal/mol). The Ramachandran plots provided by the GENO3D full model analysis reported that 98.9%, 98.4%, 94.6%, 98%, 100%, 97.9%, 100%, 98.4% of the residues fell within the allowed regions according to truncated structures: A, B, C, D, E, F, G and H respectively. Figure 3 shows the tertiary structures generated by homology modeling.

Bottom Line: Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms.The free energies were compatible with that of p16 full length original form, the full length.It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute, Tehran, Iran.

ABSTRACT
Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G(1)-S phase restriction point and p16(INK4a), a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

No MeSH data available.


Related in: MedlinePlus