1Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran
2Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran.
3Protein Chemistry Laboratory (PCL), Department of Biology, Shiraz University, Shiraz 71454, Iran.
Disposition and transportation of anticancer drugs by human serum albumin (HSA) affects their bioavailability, distribution and elimination. In this study, the interaction of a set of anticancer drugs with HSA was investigated by molecular dynamics and molecular docking simulations. The drugs' activities were analyzed according to their docking scores, binding sites and structural descriptors. The results displayed the ability of cavity 1, located in the cleft between domains I and III, to potentiate as the principal binding site of all tested drugs. This cavity provides a large space without any effective steric hindrance and induces the stability of the drugs in their binding sites by short and long ranged interactions with the accessible residues. Yet, specific structural features may lead some drug configurations to advance stronger interactions with cavities other than cavity 1. Also, the small volume and position of some cavities i.e. cavities 3, 5-10 involve penetration, small molecular volume and specific geometry which consequently force most drugs out of the corresponding binding sites. Therefore, the steric factor seems to play the most important role in the transportation of drugs by HSA.
Li Y, He WY, Liu H, Yao X, Hu Z. Daidzein interaction with human serum albumin studied using optical spectroscopy and molecular modeling methods. J Mol Struc 2007; 831:144-150.
Varshney A, Sen P, Ahmad E, Rehan M, Subbarao N, Khan RH. Ligand binding strategies of human serum albumin: How can the cargo be utilized? Chirality 2010;22: 77-87.
Falé PLV, Ascensão L, Serralheiro MLM, Haris PI. Interaction between Plectranthus barbatus herbal tea components and human serum albumin and lysozyme: Binding andactivity studies. Spectroscopy 2011;26:79-92.
Abu-Surrah AS, Kettunen M. Platinum Group Antitumor Chemistry: Design and development of New Anticancer Drugs Complementary to Cis-platin. Cur Med Chem 2006; 13:1337-1357.
Cohen S, Margalit R. Binding of porphyrin to human serum albumin: Structure-activity relationships. J Biochem 1990;270:325-330.
Dezhampanah H, Bordbar AK, Farshad S. Thermodynamic characterization of phthalocyanine–human serum albumin interaction. Spectroscopy 2011;25:235-242.
He X M, Carter DC. Atomic structure and Chemistry of human serum albumin. Nature 1992; 358:209-215.
Sudlow G, Birkett DJ, Wade DN. Further characterization of specific drug binding sites on human serum albumin. Mol Pharmacol 1976;12:1052-1061.
Sjoholm I, Ekman B, Kober A, Ljungstedt-Pahlman I, Seiving B, Sjodin T. Binding of drugs to human serum albumin: XI. The specificity of three binding sites as studied with albumin immobilized in microparticles. Mol Pharmacol 1979;16:767-777.
Tian J, Liu J, Xie J, Yao X, Hu Z, Chen X. Binding of wogonin to human serum albumin: a common binding site of wogonin in subdomain IIA. J Photochem Photobio B: Bio 2004;74: 39-45.
Radin NS. Meta-analysis of anticancer drug structures - significance of their polar allylic moieties, anti-cancer agents in medicinal chemistry. Anti-Cancer Agents 2007;7:209-222.
Watanabe H, Ikesue H, Yoshida M, Yamamoto N, Sakamoto RNS, Koga T, Sueyasu M, Egashira N, Inoshima I, Nakanishi Y, Oishi R. Protection against the extravasation of anticancer drugs by standardization of the management system. Hos Pharm 2008;43:571-576.
Yi-Lwern Yap K, Kuo EY, Jun Jie Lee J, Chui WK, Chan A. An onco informatics database for anticancer drug interactions with complementary and alternative medicines used in cancer treatment and supportive care: an overview of the OncoRx project. Supp Care in Cancer 2010;18:883-891.
Hurria L, Balducci A. Geriatric Oncology, in: B.S. Mohile S, Nagovskiy N, Balducci L (Eds.), Chemotherapy for the older adult with cancer. Springer USA 2009; pp:201-261.
Newman DJ, Cragg GM. The discovery of anticancer drugs from natural sources. Nat Products 2005;3:129-168.
HyperChem, Release 7.0 for windows, Hypercube, Inc., 2002.
Berendsen HJC, van der Spoel D, van Drunen R. GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun 1995;91:43-56.
Lindahl E, Hess B, van der Spoel D. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 2001;7:306-317.
van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. GROMACS: fast, flexible and free. J Comput Chem 2005;26:1701-1719.
Ghuman, J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry S. Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol 2005;353:38.
van Gunsteren WF, Billeter SR, Eising AA, Huenberger PH, Kruger P, Mark AE, Scott WRP, Tironi IG. Biomolecular simulation: the GROMOS 96 manual and user guide; Switzerland: 1996.
Darden T, York D, Pedersen L. Particle mesh Ewald-an NlogN method for Ewald sums in large systems. J Chem Phys 1993;98:10089-10092.
Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. A smooth particle mesh Ewald method. J Chem Phys 1995;103:8577-8593.
Kennard EH, Earle HK. Kinetic theory of gases: with an introduction to statistical mechanics. McGraw-Hill, New York; 1938.
Huang K. Statistical mechanics. Wiley, New York; 1963.
Swope WC, Andersen HC, Berens PH, Wilson KR. A computer simulation method for the calculation of equilibrium constants for the formation of physical clusters of molecules: application to small water clusters. J Chem Phys 1982;76:637-649.
Berendsen HJC, Postma JPM, Van Gunstetren WF, Hermans J. Interaction models for water in relation to protein hydration. In: Pullman B (ed) Intermolecular forces. Reidel, Dordrecht, Netherlands, 1981;331-342.