title: An in silico approach to map the binding site of doxorubicin on hemoglobin.
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.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Shahper Nazeer
authors.initials: SN
authors.lastname: Khan
authors.forename: Asad Ullah
authors.initials: AU
authors.lastname: Khan
references.citation: J Comput Aided Mol Des. 2002 Nov;16(11):795-801
references.pmid: 12825791
references.citation: J Colloid Interface Sci. 2006 Apr 1;296(1):324-31
references.pmid: 16225884
references.citation: Chem Biol Interact. 1972 May;4(6):409-19
references.pmid: 5030586
references.citation: Curr Opin Allergy Clin Immunol. 2001 Aug;1(4):317-25
references.pmid: 11964707
references.citation: Biochim Biophys Acta. 1998 Mar 6;1370(1):31-40
references.pmid: 9518541
references.citation: Hemoglobin. 1980;4(5-6):735-45
references.pmid: 6254923
references.citation: Biochem J. 1979 Jun 1;179(3):665-73
references.pmid: 475774
references.citation: Blood. 1978 Nov;52(5):878-85
references.pmid: 698394
references.citation: Adv Colloid Interface Sci. 2005 Nov 30;116(1-3):111-20
references.pmid: 16099417
references.citation: Braz J Med Biol Res. 2003 Dec;36(12):1643-51
references.pmid: 14666248
references.citation: J Biol Chem. 1962 Apr;237:1319-22
references.pmid: 14473857
references.citation: J Mol Biol. 1982 Oct 25;161(2):269-88
references.pmid: 7154081
references.citation: Am J Hematol. 1979;7(2):97-106
references.pmid: 539595
references.citation: Tohoku J Exp Med. 2007 Sep;213(1):1-16
references.pmid: 17785948
references.citation: Annu Rev Pharmacol Toxicol. 1997;37:91-117
references.pmid: 9131248
references.citation: Crit Rev Oncol Hematol. 1991;11(1):43-64
references.pmid: 1831987