Docking Studies of Competitive Interaction of Human Serum Albumin

With Ibuprofen and Aspirin Using the HEX Docking Software

Aim: Computational method of analysis using Hex docking to find out the good interacting
molecule.
Introduction:
Human serum albumin (HSA) the main protein component of plasma, accounts for about 0%
of the plasmas total protein contents, and contains three homologous helical domains (IIII),
each divided into A and B sub domains. The binding of drugs with serum albumin plays an
important role in the study of the bioavailability, efficacy, transport and toxicity of the drugs.
Many drugs bind to serum albumin at one of two primary sites (I and II) located in sub
domains IIA and IIIA, respectively. The investigation of the interaction of drugs and serum
albumin appeals lots of interests. Non-steroidal anti-inflammatory drugs have been widely
used in the pharmaceutical field as the performances of treating inflammation, pain and fever,
especially in the treatment and prevention of Parkinsons disease (PD)and Alzheimers
disease (AD) Ibuprofen (Ibu) and aspirin (acetyl salicylic acid (ASA))their derivatives are
used commonly as analgesic and anti-inflammatory drugs in clinical medicine. Some
researchers studied the binding where legand (the drug and the competitor) share the same
binding site on the protein Computer-aided drug design (CADD) is a rapidly evolving field
that leverages new data and methods to provide approaches for tackling the needs of drug
discovery. One such method is the docking of the drug molecule with the receptor (target).
The site of drug action, which is ultimately responsible for the pharmaceutical effect, is a
receptor. Docking is the process by which two molecules fit together in 3D space.
Principle:
Computational methods are playing increasingly larger and more important role in drug
discovery and development and are believed to offer means of improved efficiency for the
industry. Serum albumin is the most abundant protein in blood plasma. The binding of drugs
with serum albumin plays an important role in the study of the bioavailability, efficacy,
transport and designing of the drugs. Two typical non-steroidal anti-inflammatory drugs are
ibuprofen, and aspirin which used commonly as analgesic drug in clinical medicine and
sometimes are co-administered. Docking is conducted by a procedure involving multiple
conformer shape-matching alignment of a molecule to a cavity followed by energy
minimization on both the molecule and the protein residues at the binding region.

Structure of human serum albumin (HAS) PDB code 1N5U


Structure of a) Ibuprofen (Ibu), b) Aspirin (acetyl salicylic acid (ASA))
Procedure:
Find the macromolecular target protein structure ID 1N5U from pdb database and
download ,save the molecule in Pdb format
Draw or find the drug molecular structure from PubChem compound database from
NCBI
SAVE the molecule in SDF format
Change the SDF file format of small drug molecule into .pdb format using any
molecular converter.
Start Hex software upload target macromolecule into Hex interface
Upload small drug molecule in pdb format into Hex
Select docking interface to activate the docking process.
Before to start the docking process define the active site to where the drug molecule
has to be bind on the target molecule.
Find out the target active site through PDBSUM server .and take the list of amino acid
which is present in the active site.
Start to activate the docking process and dismiss the mechanism
After few minutes observe the energy and e model score to con form the dock
between macro and small drug molecule.
Report the result
Result:
In this study, HSA which is main protein component of plasma was used for docking-binding
interactions studies with ibuprofen and aspirin. The results showed that the docking between
al HSA and Ibu had interaction having energy value of --------------. When the ASA was
docked against the receptor the energy value obtained was found to be------------------------.