The structures of two chosen compounds were drawn using Hyperchem7 software and
Gaussian 2003 33. Force field parameters and geometries of the ligands were generated
using PRODRG2 server 34, and they were changed to be adaptable to the preferred
force field. The MD simulations were
performed by the GROMOS 43A1 force field and TIPP4 model 35 was used for
water molecules. A twin range cutoff was used for long-range interactions: 0.9 nm for van der Waals interactions
and 0.9 nm for electrostatic interactions. The PME 36 was used for
calculating long-range interaction. The starting structure of BuChE was
constructed based upon the X-ray crystal structure of it (PDB
ID: 2WIJ). A cubic simulation box of the volume 315 nm3 was made, and eight molecules of an inhibitor were
placed randomly in this box respectively. Then water molecules were haphazardly
added to the simulation box, and initial configurations were
minimized using the steepest descent algorithm with 5000
integration step, and the system was equilibrated for 20 ns at constant
pressure (1 atm) and temperature (300 K) using the Parilleno-Rahman procedure.
All MD simulations were carried out using the GROMACS 4.5.4 package 37.
were performed using 5quad core parallel computers, including 40 processor
units. The computer applied the Rocks cluster networking and CentOS operating systems. The four molecules of two inhibitors
were used in the 16867, 16791 and 16747 water molecules for 2wij, 5e, and 8e,
respectively in a box has size 7.865, 7.764, 9.543 nm3. Data analysis. The
conformational changes of the system during MD simulations were monitored by
the root-mean-square derivations (RMSD) as follows;
Where mi is the mass
of atoms, rio and ri are the coordinates
of i atom at the reference state and during MD simulations, respectively.
RMSDs were calculated for the trajectories from the starting structures of the
system as a function of time. In all systems, RMSDs reach a stable value within
the first nanosecond of all the analyses.
The radial distribution function g(r)
is the density probability for finding a particle at distance r from the reference particle. The g(r) between particles of type A and B
is defined as follows:
length. Solvent accessible surface area of protein was also computed by this program. Accessible
surface area, helix percentage, hydrogen bond, angle information and other
complementary information were obtained by VADAR 38.