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An in silico approach to map the binding site of doxorubicin on hemoglobin.

Khan SN, Khan AU - Bioinformation (2008)

Bottom Line: The best conformation was sought by employing GOLDV.The interaction was found to be thermodynamically favorable (DeltaG degrees = -66.23 KJmol(-1)).The analysis of DOX binding site to Hb suggested that the types of interactions that contribute in this binding are hydrophobic contacts, hydrogen bonding and electrostatic interactions.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.

ABSTRACT
Binding modalities of doxorubicin (DOX), a widely used antineoplastic anthracyline antibiotic with hemoglobin (Hb) have been studied. The protein and the ligand were prepared using CORINA and protonated with insight II. The best conformation was sought by employing GOLDV. Molecular modeling calculations showed that DOX binds Hb to a non-classical drug binding site. The alpha subunit of Hb has been assigned to posses the binding site for DOX with a binding affinity (Ka) = 16.98 x10(3) mol(-1). The interaction was found to be thermodynamically favorable (DeltaG degrees = -66.23 KJmol(-1)). The analysis of DOX binding site to Hb suggested that the types of interactions that contribute in this binding are hydrophobic contacts, hydrogen bonding and electrostatic interactions.

No MeSH data available.


Two dimensional structure of doxorubicin downloaded from PubChem (pubchem.ncbi.nlm.nih.gov).
© Copyright Policy - open-access
Related In: Results  -  Collection


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Figure 1: Two dimensional structure of doxorubicin downloaded from PubChem (pubchem.ncbi.nlm.nih.gov).

Mentions: Known crystal structures of oxy-Hemoglobin (Hb) (PDB Id: 1HHO) was obtained from the Brookhaven Protein Data Bank. The two dimensional (2D) structure of DOX (Figure 1) was downloaded from Pubchem (pubchem.ncbi.nlm.nih.gov). 2D to 3D conversion was done using CORINA [13]. Water molecules and ions were removed (including ordered water molecules) and hydrogen atoms were added at appropriate geometry. Groups within the protein were ionized as required at physiological pH. The structure of Hb was protonated using Insight II (www.accelrys.com). The genetic algorithm was implemented in GOLDv3.1.1 that was applied to calculate the possible conformations of the drug binding to protein. The genetic algorithm parameters used in the analysis include, population size 100, number of islands 5, niche size 2, selection pressure 1.1, migrate 2; number of operators 100,000, mutate 95 and crossover 95. A maximum of 10 different conformations was considered for the drug during the docking process. The conformer with the lowest binding free energy was used for further analysis.


An in silico approach to map the binding site of doxorubicin on hemoglobin.

Khan SN, Khan AU - Bioinformation (2008)

Two dimensional structure of doxorubicin downloaded from PubChem (pubchem.ncbi.nlm.nih.gov).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2533059&req=5

Figure 1: Two dimensional structure of doxorubicin downloaded from PubChem (pubchem.ncbi.nlm.nih.gov).
Mentions: Known crystal structures of oxy-Hemoglobin (Hb) (PDB Id: 1HHO) was obtained from the Brookhaven Protein Data Bank. The two dimensional (2D) structure of DOX (Figure 1) was downloaded from Pubchem (pubchem.ncbi.nlm.nih.gov). 2D to 3D conversion was done using CORINA [13]. Water molecules and ions were removed (including ordered water molecules) and hydrogen atoms were added at appropriate geometry. Groups within the protein were ionized as required at physiological pH. The structure of Hb was protonated using Insight II (www.accelrys.com). The genetic algorithm was implemented in GOLDv3.1.1 that was applied to calculate the possible conformations of the drug binding to protein. The genetic algorithm parameters used in the analysis include, population size 100, number of islands 5, niche size 2, selection pressure 1.1, migrate 2; number of operators 100,000, mutate 95 and crossover 95. A maximum of 10 different conformations was considered for the drug during the docking process. The conformer with the lowest binding free energy was used for further analysis.

Bottom Line: The best conformation was sought by employing GOLDV.The interaction was found to be thermodynamically favorable (DeltaG degrees = -66.23 KJmol(-1)).The analysis of DOX binding site to Hb suggested that the types of interactions that contribute in this binding are hydrophobic contacts, hydrogen bonding and electrostatic interactions.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.

ABSTRACT
Binding modalities of doxorubicin (DOX), a widely used antineoplastic anthracyline antibiotic with hemoglobin (Hb) have been studied. The protein and the ligand were prepared using CORINA and protonated with insight II. The best conformation was sought by employing GOLDV. Molecular modeling calculations showed that DOX binds Hb to a non-classical drug binding site. The alpha subunit of Hb has been assigned to posses the binding site for DOX with a binding affinity (Ka) = 16.98 x10(3) mol(-1). The interaction was found to be thermodynamically favorable (DeltaG degrees = -66.23 KJmol(-1)). The analysis of DOX binding site to Hb suggested that the types of interactions that contribute in this binding are hydrophobic contacts, hydrogen bonding and electrostatic interactions.

No MeSH data available.