Electronic structure and partial charge distribution of doxorubicin under different molecular environments
Date
2014Metadata
[+] Show full item recordAbstract
Doxorubicin (trade name Adriamycin, abbreviated DOX) is a well-known anthracyclic chemotherapeutic used in treating a variety of cancers including acute
leukemia, lymphoma, multiple myeloma, and a range of stomach, lung, bladder, bone,
breast, and ovarian cancers. The purpose of the present work is to study electronic
structure, partial charge distribution and interaction energy of DOX under different
environments. It provides a framework for better understanding of bioactivity of DOX
with DNA. While in this work, we focus on DOX-DNA interactions; the obtained
knowledge could be translated to other drug-target interactions or biomolecular interactions.
The electronic structure and partial charge distribution of DOX in three different
molecular environments: isolated, solvated, and intercalated into a DNA complex,
were studied by first principles density functional methods. It is shown that the addition of solvating water molecules to DOX and the proximity and interaction with
DNA has a significant impact on the electronic structure as well as the partial charge
distribution. The calculated total partial charges for DOX in the three models are
0.0, +0.123 and -0.06 electrons for the isolated, solvated, and intercalated state, respectively. Furthermore, by using the more accurate ab initio partial charge values
on every atom in the models, significant improvement in estimating the DOX-DNA
interaction energy is obtained in conjunction with the NAnoscale Molecular Dynamics (NAMD) code. The electronic structure of the DOX-DNA is further elucidated
by resolving the total density of states (TDOS) into different functional groups of
DOX, DNA, water, co-crystallized Spermine molecule, and Na ions. The surface
partial charge distribution in the DOX-DNA is calculated and displayed graphically.
We conclude that the presence of the solvent as well as the details of the interaction
geometry matter greatly in the determination of the stability of the DOX complexion. Ab initio calculations on realistic models are an important step towards a more
accurate description of biomolecular interaction and in the eventual understanding of
long-range interactions in biomolecular systems.
Table of Contents
Introduction -- Theoretical background -- Results and discussions -- Appendix A. VASP input files -- Appendix B. Abbreviations
Degree
M.S.