w**r
发帖数: 134 | 1 我见的最多的是七个人，这样七个人都是可以认为第一作者了 | l**********1
发帖数: 5204 | 2 人家各做一个residue 3D
Molecular Modeling 的话 还是可能的
//www.ncbi.nlm.nih.gov/pubmed/22448988
Crystal structures of Bcl-xL with 118 (PDB entry 2YXJ) and 4 were used to
model the binding poses of our designed compounds with Bcl-xL. In the
binding models, the structure of Bcl-xL in complex with 4 was superimposed
on that of Bcl-xL in complex with 1. The core scaffold of 4 then replaced
the 4′-chloro-2-methyl-1,1′-biphenyl group of 1 to generate the initial
binding model, which was then refined by a 1 ns molecular dynamics (MD)
simulation. All the modifica- tions of the ligands were performed by the
Sybyl program.28
The charge and force field parameters of the compounds
were obtained with the most recent Antechamber module in
the Amber 10 program suite,29 where the charge models were
calculated from the Gaussian 98 program30 at the Hartree−
Fock level by use of the 6-31G** basis sets. Protocols for the
MD simulation are the following. The total charge of the sys-
tem was neutralized by first adding counterions. Then, the
system was solvated in a 10 Å cubic box of water by use of the
TIP3P water model.31 Two thousand steps of minimization
of the system were performed where the protein and the
modeled compound were constrained by a force constant of
50 kcal·mol−1·Å−2. After minimization, a 20 ps
simulation was
used to gradually raise the temperature of the system to 298 K
while the whole system was constrained by a force constant of
10 kcal·mol−1·Å−2. Another 40 ps of equilibrium run was
used
atoms were constrained by a force constant of 2 kcal·mol ·Å .
A final production run of 1 ns was performed with no con- straints on any
atoms of the complex structure. When con- straints were applied, the initial
complex structure was used as a reference structure. All the MD simulations
were at NTP. The SHAKE algorithm32 was used to fix the bonds involving
hydrogen. The PME method33 was used and the nonbonded cutoff distance was
set at 10 Å. The time step was 2 fs, and the neighboring pairs list
was updated in every 20 steps.
Final conformations of Bcl-xL in complex with 6 and 7 are shown in bla bla
ba... | n******7
发帖数: 12463 | |
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