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.
Highlights
It is well established that free molecules of drug can act at the target site
The computational modeling was used to identify the amino acids involved in binding site
Genetic algorithm Genetic algorithm (GA) is a computer program that mimics the process of evolution by manipulating a collection of datastructures called chromosomes
Summary
It is well established that free molecules of drug can act at the target site. This is because free drugs are rapidly distributed into tissues, which facilitate direct binding to tissue proteins. The computational modeling was used to identify the amino acids involved in binding site It can predict various conformational states of bio-molecules such as the oxygen bound form of Hb as described in the present study. The scoring functions have all the necessary elements that correspond to the non-covalent interactions in a conventional force field, such as the van der Waals interaction and the electrostatic interaction It considers the hydrophobic effect and provides a better estimation of binding free energies. The hydrogen-bonding or electrostatic interaction acts as an anchor and this helps to attain the 3D space position of DOX in its binding pocket This facilitates the hydrophobic interaction of the dihydroxyanthraquinone rings with the side chain of Hb residues. It has been shown that the interaction of DOX with Hb induced a significant increase (22%) in oxygen affinity as compared with Hb without drug [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
