Molecular dynamics simulation studies of betulinic acid with human serum albumin

Chandramouli Malleda, Navjeet Ahalawat, Mahesh Gokara, Rajagopal Subramanyam

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Betulinic acid (BA) is a naturally occurring pentacyclictriterpenoid possessing anti-retroviral, anticancer, and anti-inflammatory properties. Here, we studied the interaction of BA with human serum albumin (HSA) by using molecular docking, and molecular dynamic simulation methods. Molecular docking studies revealed that BA can bind in the large hydrophobic cavity of drug binding site I of sub-domain IIA and IIB, mainly by the hydrophobic interactions and also by hydrogen bond interactions. In which several cyclohexyl groups of BA are interacting with Phe (206), Arg(209), Ala(210), Ala(213), Leu(327), Gly(328), Leu(331), Ala(350), and Lys(351), residues of sub-domain IIA and IIB of HSA by hydrophobic interactions. Also, hydrogen bond interactions were observed between the hydroxyl (OH) group of BA with Phe(206) and Glu(354) of HSA, with hydrogen bond distances of 0.24 nm,0.28 nm respectively. Further, specifically, the molecular dynamics study makes an important contribution in understanding the effect of the binding of BA on conformational changes of HSA and the stability of the protein-drug complex system in aqueous solution. The root mean square deviation values of atoms in the free HSA molecule were calculated from 3000 ps to 5000 ps trajectory and the results were obtained as 0.72± 0.036 nm and 0.81±0.032 nm for free HSA and HSA-BA, respectively. The radius of gyration (Rg) values of both unliganded HSA and HSA-BA were stabilized at 2.59± 0.03 nm, 2.51±0.01 nm, respectively. Thus, this work may play an important role in the design of new BA inspired drugs with desired HSA binding affinity.

Original languageEnglish
Pages (from-to)2589-2597
Number of pages9
JournalJournal of Molecular Modeling
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Betulinic acid
  • Docking
  • Human serum albumin
  • Molecular dynamics

ASJC Scopus subject areas

  • Catalysis
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Computational Theory and Mathematics
  • Inorganic Chemistry

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