Results

Movies

Molecular Dynamics

MR-AS4 MD simulation

Mineralocorticoid (MR-wt/MRS810) protein interaction with Aldosteron (AS4) ligand

MR-COL MD simulation

Mineralocorticoid (MR-wt/MRS810L) protein interaction with Cortisol (COL) ligand

MR-STR MD simulation

Mineralocorticoid (MR-wt/MRS810L) protein interaction with progesterone (STR) ligand

MRdimer-AS4 MD simulation

Mineralocorticoid dimer (MRdiemr) protein interaction with Aldosterone (AS4) ligand

Monte Carlo

MR-AS4 MC simulation

Monte Carlo simulation of mineralocorticoid (MR) protein interacting with Aldosteron (AS4) ligand

Images

Molecular Dynamics

MD MR-AS4 energies
MD MR-AS4 energies

Monte Carlo

MC MR-AS4 energies as function of RMSD
MC MR-AS4 energies as function of RMSD
MC MR-AS4 RMSD at high temperatures
MC MR-AS4 energies as function of RMSD at high temperatures
RMSD MR-AS4 MC RMSD MR-COL MC RMSD MR-STR MC RMSD MR_S810L-AS4 MC RMSD MR_S810L-COL MC RMSD MR-STR_mut MC RMSD MR-AS4_dimer MC
MC energies

MC Table

Ligand Temperature (K) Unbinding Binding Unbiding Probability (%) Biding Probability (%)
AS4 5000K 0 1 0.00 1.96
AS4 7000K 2 20 3.92 39.22
COL 5000K 0 0 0.00 0.00
COL 7000K 0 28 0.00 54.90
STR 5000K 0 0 0.00 0.00
STR 7000K 4 30 7.84 58.82
AS4mut 5000K 0 3 0.00 5.88
AS4mut 7000K 2 30 3.92 58.82
COLmut 5000K 0 3 0.00 5.88
COLmut 7000K 0 14 0.00 27.45
STRmut 5000K 0 0 0.00 0.00
STRmut 7000K 5 19 11.76 37.25
AS4dimer 5000K 6 19 11.76 37.25
AS4dimer 7000K 92 124 180.39 243.14

All simulation have 51 samples.

PyEMMA

A better aproach to analyse these data is using PyEMMA, a Python library for the estimation, validation and analysis Markov models of molecular kinetics and other kinetic and thermodynamic models from molecular dynamics (MD) data.

States found using MC simulation and PyEMMA in the MR-AS4 system at 7000K States found using MC simulation and PyEMMA in the MR-COL system at 7000K States found using MC simulation and PyEMMA in the MR-STR system at 7000K States found using MC simulation and PyEMMA in the MR_mut-AS4 system at 7000K States found using MC simulation and PyEMMA in the MR_mut-COL system at 7000K States found using MC simulation and PyEMMA in the MR_mut-STR system at 7000K
States found in the MC simulations at 7000K using PyEMMA
Example of the states found using MC simulation and PyEMMA in the MR-AS4 system at 7000K Example of the states found using MC simulation and PyEMMA in the MR-COL system at 7000K Example of the states found using MC simulation and PyEMMA in the MR-STR system at 7000K Example of the states found using MC simulation and PyEMMA in the MR_mut-AS4 system at 7000K Example of the states found using MC simulation and PyEMMA in the MR_mut-COL system at 7000K Example of the states found using MC simulation and PyEMMA in the MR_mut-STR system at 7000K
Some examples of the states found in the MC simulations at 7000K using PyEMMA

Mean First Passage Times (MFPTs)

All Sytems, All States
Mean First Passage Times (MFPTs) analysis found for all the system at 7000 using PyEMMA
Mean First Passage Times (MFPTs) analysis found for all the system at 7000 K using PyEMMA
Bound State - Others
Ligand MFPT bound → other MFPT other → bound
Aldo 511.8 ± 8.3 34229.1 ± 5028.2
Col 512.9 ± 8.9 163482.9 ± 31149.2
Str 267.7 ± 3.3 57136.8 ± 8330.1
Aldomut 797.7 ± 16.4 38229.3 ± 5514.4
Colmut 968.2 ± 21.5 53617.9 ± 5090.8
Strmut 446.2 ± 5.5 9677.0 ± 1095.6