Sergey Shityakov and Carola Förster
Accepted Abstracts: Med Chem
Background and Aims: Human serum albumin (HSA) is one of the most abundant proteins in the circulatory system and
plays a crucial role in the transport of different drugs, metabolites, and fatty acids. Therefore, a drug binding to serum albumin
is an important parameter to determine pharmacokinetic and pharmacodynamics properties for chemical substances in the
human body. However, despite the numerous attempts to characterize the HSA binding sites involved in this process, none of
them have employed linear interaction energy method to predict binding affinities and compare them to the experimentally
determined ones. Here, we performed classical molecular dynamics (MD) simulations on general anesthetic propofol bound
to HSA to describe the drug binding affinity using linear interaction energy method.
Method: Molecular mechanics potential energy minimization and MD simulations were carried out using the program
package GROMACS v.4.5.5. The position restrained run was performed for 1.0 ns of NVT (constant volume and temperature)
ensemble dynamics to relax the water while applying restraints to the protein and equilibrate the system. The production run
was then performed at constant pressure and temperature (NPT) for 1.0 ns for ligand and 15 ns for complex and at 300 K. The
Particle-Mesh-Ewald (PME) method was used to treat long-range Coulombic interactions. The LINCS algorithm was used to
constrain bond lengths involving hydrogen?s, permitting a time step of 2 fs. Van der Waals force and Coulomb interactions were
maintained at 1.0 nm according to Kerrigan?s protocol. The trajectory files were analysed through the g_energy, g_sas, g_dist,
and g_lie GROMACS utilities in order to compute the appropriate functions. The g_lie program used the LIE equation as:
ΔGbind = α(
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