Idea of the project: comparison of the behavior of three different variants of b2m (the same we're studying in Proline Metadynamics),that are D76N (the most amyloidogenical), W60G (the anti-aggregation) and WT, once they are interacting with graphite
Main steps: docking --> 500ns classic MD --> parallel tempered Metadynamics
In the same experimental conditions used by Mangione, the three variant result protonated this way:
- WT Qtot = -2 , 13HISE(0), 31HISE (0), 51HISE (0), 84 HISE (0)
- W60G Qtot = -1 , 13HISE (0), 31HISE (0), 51HISE (0), 84HISH (+1)
- D76N Qtot = 0 , 13HISD(0), 31HISD (0), 51HISE (0), 84HISH(+1)
PQR file (containing charges and vdW radius) are requested as input for SDA 7.2 software
SDA 7.2 Simulation of Diffusional Association software
Main steps
- generate pqr files for each solute (with protonation states for the experimental conditions to be modeled)
- Compute Poisson-Boltzmann electrostatic potential grids
- Compute the effective charges (Effective Charges for Macromolecules)
- Compute the other grids: electrostatic desolvation, hydrophobic desolvation and soft-core repulsive grids
Docking production simulations with default probes probep = 1.7 probew = 1.4 ( sum =3.1 Å represents an approximation to the length of a hydrogen bond)
Result of docking clusters
Wild Type
N step cl_ size energy cl_size with SDA
1 177620 453 -6.479e+01 1.258137e+06 (intersection between LYS74 and 3layer)
2 53766 749 -7.907e+01 2.379139e+06
3 149515 5 -7.891e+01 2.476000e+04
4 43704 168 -6.940e+01 4.494750e+05
5 133836 134 -6.959e+01 4.293740e+05
6 90677 15 -6.541e+01 1.554900e+04
7 98819 18 -6.112e+01 1.312500e+04
8 25355 449 -5.951e+01 9.609290e+05
## RunNb StepNb TotEn El ED HD rLJ Occur AvEnergy StdAvEnergy
54 177620 -1.1079E+02 0.0000E+00 2.9168E+01 -1.1734E+01 -1.2823E+02 453 -6.479e+01 1.258137e+06
25 53766 -8.4132E+01 0.0000E+00 9.3869E+00 -7.9987E+00 -8.5520E+01 749 -7.907e+01 2.379139e+06
28 149515 -7.9696E+01 0.0000E+00 1.8096E+01 -1.0105E+01 -8.7687E+01 5 -7.891e+01 2 .476000e+04
20 43704 -7.2527E+01 0.0000E+00 7.7342E+00 -6.4271E+00 -7.3834E+01 168 -6.940e+01 4.494750e+05
83 133836 -7.1902E+01 0.0000E+00 9.8352E+00 -6.9440E+00 -7.4793E+01 134 -6.959e+01 4.293740e+05
34 90677 -6.5922E+01 0.0000E+00 9.0404E+00 -6.0320E+00 -6.8931E+01 15 -6.541e+01 1.554900e+04
77 98819 -6.3945E+01 0.0000E+00 2.1447E+01 -7.9523E+00 -7.7440E+01 18 -6.112e+01 1.312500e+04
38 25355 -6.0649E+01 0.0000E+00 8.7353E+00 -6.3685E+00 -6.3016E+01 449 -5.951e+01 9.609290e+05