[gmx-users] Umbrella Sampling - Ligand Protein

[Steven Neumann]

Dear Gmx Users, Dear Justin,

I pulled my ligand away from my protein. Ligand was attached to lower part
of my protein, I pulled in Z coordinate it using:

; Run parameters

integrator = md ; leap-frog integrator

nsteps = 5000000 ; 2 * 5000000 = 10 ns

dt = 0.002 ; 2 fs

tinit = 0

nstcomm = 10

; Output control

nstxout = 50000 ; save coordinates every 100 ps

nstvout = 50000 ; save velocities every

nstfout = 5000

nstxtcout = 5000 ; every 10 ps

nstenergy = 5000

; Bond parameters

continuation = yes ; first dynamics run

constraint_algorithm = lincs ; holonomic constraints

constraints = all-bonds ; all bonds (even heavy atom-H bonds) constrained

; Neighborsearching

ns_type = grid ; search neighboring grid cells

nstlist = 5 ; 10 fs

rlist = 0.9 ; short-range neighborlist cutoff (in nm)

rcoulomb = 0.9 ; short-range electrostatic cutoff (in nm)

rvdw = 0.9 ; short-range van der Waals cutoff (in nm)

ewald_rtol = 1e-5 ; relative strenght of the Ewald-shifted potential
rcoulomb

; Electrostatics

coulombtype = PME ; Particle Mesh Ewald for long-range electrostatics

pme_order = 4 ; cubic interpolation

fourierspacing = 0.12 ; grid spacing for FFT

fourier_nx = 0

fourier_ny = 0

fourier_nz = 0

optimize_fft = yes

; Temperature coupling is on

tcoupl = V-rescale ; modified Berendsen thermostat

tc_grps = Protein_LIG Water_and_ions ; two coupling groups - more accurate

tau_t = 0.1 0.1 ; time constant, in ps

ref_t = 298 298 ; reference temperature, one for each group, in K

; Pressure coupling is on

pcoupl = Parrinello-Rahman ; pressure coupling is on for NPT

pcoupltype = isotropic ; uniform scaling of box vectors

tau_p = 1.0 ; time constant, in ps

ref_p = 1.0 ; reference pressure, in bar

compressibility = 4.5e-5 ; isothermal compressibility of water, bar^-1

; Periodic boundary conditions

pbc = xyz ; 3-D PBC

; Dispersion correction

DispCorr = EnerPres ; account for cut-off vdW scheme

; Velocity generation

gen_vel = no ; assign velocities from Maxwell distribution

; These options remove COM motion of the system

; Pull code

pull = umbrella

pull_geometry = distance

pull_dim = N N Y

pull_start = yes

pull_ngroups = 1

pull_group0 = Protein

pull_group1 = LIG182

pull_init1 = 0

pull_rate1 = 0.0

pull_k1 = 200 ; kJ mol^-1 nm^-2

pull_nstxout = 1000 ; every 2 ps

pull_nstfout = 1000 ; every 2 ps

Following Justin's tutorial I used perl script to extract coordinate for
each window.

0       2.4595039

1       2.4745028

...

500    8.74

My ligand at the begining was at such distance as it was in the lower part
of the protein. Then I used 0.1 nm spacing at the begining (till 4 nm) and
0.2 nm later on.

And following equilibration in each window I run umbrella sampling for 10ns
in app 49 windows:

Run parameters

integrator = md ; leap-frog integrator

nsteps = 5000000 ; 2 * 5000000 = 10 ns

dt = 0.002 ; 2 fs

tinit = 0

nstcomm = 10

; Output control

nstxout = 50000 ; save coordinates every 100 ps

nstvout = 50000 ; save velocities every

nstfout = 5000

nstxtcout = 5000 ; every 10 ps

nstenergy = 5000

; Bond parameters

continuation = yes ; first dynamics run

constraint_algorithm = lincs ; holonomic constraints

constraints = all-bonds ; all bonds (even heavy atom-H bonds) constrained

; Neighborsearching

ns_type = grid ; search neighboring grid cells

nstlist = 5 ; 10 fs

rlist = 0.9 ; short-range neighborlist cutoff (in nm)

rcoulomb = 0.9 ; short-range electrostatic cutoff (in nm)

rvdw = 0.9 ; short-range van der Waals cutoff (in nm)

ewald_rtol = 1e-5 ; relative strenght of the Ewald-shifted potential
rcoulomb

; Electrostatics

coulombtype = PME ; Particle Mesh Ewald for long-range electrostatics

pme_order = 4 ; cubic interpolation

fourierspacing = 0.12 ; grid spacing for FFT

fourier_nx = 0

fourier_ny = 0

fourier_nz = 0

optimize_fft = yes

; Temperature coupling is on

tcoupl = V-rescale ; modified Berendsen thermostat

tc_grps = Protein_LIG Water_and_ions ; two coupling groups - more accurate

tau_t = 0.1 0.1 ; time constant, in ps

ref_t = 298 298 ; reference temperature, one for each group, in K

; Pressure coupling is on

pcoupl = Parrinello-Rahman ; pressure coupling is on for NPT

pcoupltype = isotropic ; uniform scaling of box vectors

tau_p = 1.0 ; time constant, in ps

ref_p = 1.0 ; reference pressure, in bar

compressibility = 4.5e-5 ; isothermal compressibility of water, bar^-1

; Periodic boundary conditions

pbc = xyz ; 3-D PBC

; Dispersion correction

DispCorr = EnerPres ; account for cut-off vdW scheme

; Velocity generation

gen_vel = no ; assign velocities from Maxwell distribution

; These options remove COM motion of the system

; Pull code

pull = umbrella

pull_geometry = distance

pull_dim = N N Y

pull_start = yes

pull_ngroups = 1

pull_group0 = Protein

pull_group1 = LIG182

pull_init1 = 0

pull_rate1 = 0.0

pull_k1 = 200 ; kJ mol^-1 nm^-2

pull_nstxout = 1000 ; every 2 ps

pull_nstfout = 1000 ; every 2 ps



My PMF profile:

http://speedy.sh/zerqZ/profile.JPG

My histogram: http://speedy.sh/PyhnN/Histo.JPG

Why g_wham takes into account distances below 2.45 nm as the 1st structure
was at 2.45. If I get rid of the distances below 2.45 (those weird values
PMF values) I obtain beautiful profile:

http://speedy.sh/TUXGC/profile1.JPG

Please, explain!

Steven
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