def test_statistical_inefficiency_multiple():
X, Y, energy = generate_data()
timeseries.statisticalInefficiencyMultiple(X)
timeseries.statisticalInefficiencyMultiple(X ** 2)
timeseries.statisticalInefficiencyMultiple(X[0, :] ** 2)
timeseries.statisticalInefficiencyMultiple(X[0:2, :] ** 2)
timeseries.statisticalInefficiencyMultiple(energy)
def test_statistical_inefficiency_multiple():
X, Y, energy = generate_data()
timeseries.statisticalInefficiencyMultiple(X)
timeseries.statisticalInefficiencyMultiple(X**2)
timeseries.statisticalInefficiencyMultiple(X[0, :]**2)
timeseries.statisticalInefficiencyMultiple(X[0:2, :]**2)
timeseries.statisticalInefficiencyMultiple(energy)
0, trajectory_segment_length)
for k in range(K):
# Determine which replica generated the data from temperature k at this iteration
replica_index = replica_ik[iteration, k]
# Reconstruct portion of replica trajectory.
U_kt_replica[replica_index,
snapshot_indices] = U_kt[k, snapshot_indices]
phi_kt_replica[replica_index,
snapshot_indices] = phi_kt[k, snapshot_indices]
psi_kt_replica[replica_index,
snapshot_indices] = psi_kt[k, snapshot_indices]
# Estimate the statistical inefficiency of the simulation by analyzing the timeseries of interest.
# We use the max of cos and sin of the phi and psi timeseries because they are periodic angles.
# The
print "Computing statistical inefficiencies..."
g_cosphi = timeseries.statisticalInefficiencyMultiple(
numpy.cos(phi_kt_replica * numpy.pi / 180.0))
print "g_cos(phi) = %.1f" % g_cosphi
g_sinphi = timeseries.statisticalInefficiencyMultiple(
numpy.sin(phi_kt_replica * numpy.pi / 180.0))
print "g_sin(phi) = %.1f" % g_sinphi
g_cospsi = timeseries.statisticalInefficiencyMultiple(
numpy.cos(psi_kt_replica * numpy.pi / 180.0))
print "g_cos(psi) = %.1f" % g_cospsi
g_sinpsi = timeseries.statisticalInefficiencyMultiple(
numpy.sin(psi_kt_replica * numpy.pi / 180.0))
print "g_sin(psi) = %.1f" % g_sinpsi
# Subsample data with maximum of all correlation times.
print "Subsampling data..."
g = numpy.max(numpy.array([g_cosphi, g_sinphi, g_cospsi, g_sinpsi]))
indices = timeseries.subsampleCorrelatedData(U_kt[k, :], g=g)
print "Using g = %.1f to obtain %d uncorrelated samples per temperature" % (
heavyIndices = np.array(heavyIndices)
cuIndices = np.array(cuIndices)
#Load in the potential energies, INCLUDING RESTRAINT, at all states for this simulation to figure out frames to skip
alcDat = np.loadtxt(alchemicalFile)
startTime = alcDat[0, 1]
startFrame = int(
startTime
) - 1 #Be careful here... need write frequency in alchemical file to match exactly with positions
#AND assuming that have written in 1 ps increments...
#Also, first frame in trajectory is NOT at time zero, so subtract 1
if endTime == -1:
thisPot = alcDat[:, 3:-1]
else:
thisPot = alcDat[:endTime, 3:-1]
thisg = timeseries.statisticalInefficiencyMultiple(thisPot)
print("Statistical inefficiency for this set of potential energies: %f" %
thisg)
#print(startTime)
#print(startFrame)
#print(thisPot.shape)
#Next load in the trajectory and get all solute coordinates that matter
top.rb_torsions = pmd.TrackedList([])
top = pt.load_parmed(top, traj=False)
if endTime == -1:
traj = pt.iterload(trajFile, top, frame_slice=(startFrame, -1))
else:
traj = pt.iterload(trajFile,
top,
if __name__ == "__main__" :
var=numpy.ones(N)
for replica in xrange(2,K+1):
var=numpy.concatenate((var,numpy.ones(N)))
X=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))/10.0
Y=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))
# X=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))
# Y=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))
# print "X.shape = "
# print X.shape
energy = 10*(X**2)/2.0 + (Y**2)/2.0
print "statisticalInefficiencyMultiple(X)"
print timeseries.statisticalInefficiencyMultiple(X)
print "statisticalInefficiencyMultiple(X**2)"
print timeseries.statisticalInefficiencyMultiple(X**2)
print "statisticalInefficiencyMultiple(X[0,:]**2)"
print timeseries.statisticalInefficiencyMultiple(X[0,:]**2)
print "statisticalInefficiencyMultiple(X[0:2,:]**2)"
print timeseries.statisticalInefficiencyMultiple(X[0:2,:]**2)
print "statisticalInefficiencyMultiple(energy)"
print timeseries.statisticalInefficiencyMultiple(energy)
# Exit with success.
# TODO: Add some checks to test statistical inefficinecies are within normal expected range.
sys.exit(0)
def summarize_timeseries(concentrations):
"""
Use boostrap sampling together with statisticalInefficiencyMultiple to calculate the mean correlation function and
its 95% confidence intervals as well as the estimated autocorrelation time.
Parameters
----------
concentrations: np.ndarray
Arrays with different time series data in each row.
Returns
-------
mean_corr_func, lower, upper: numpy.ndarray
the mean, 5th percentile, and 97.5 percentile of the estimated autocorrelation function.
auto_corr_time_mean, auto_corr_time_std
the mean autocorrelation time with its standard error.
"""
boot_samples = 50
auto_corr_time = np.zeros(boot_samples)
corr_data = []
for sample in range(boot_samples):
ints = np.random.choice(3, 3)
concs = [
concentrations[ints[0], :], concentrations[ints[1], :],
concentrations[ints[2], :]
]
g, c = timeseries.statisticalInefficiencyMultiple(
concs, return_correlation_function=True, fast=False)
auto_corr_time[sample] = (g - 1) / 2.0
corr_data += c
# The correlation time may be computed up to a different maximum time for different bootstrap samples.
# Finding the maximum time.
max_time = 0
for tup in corr_data:
if tup[0] > max_time:
max_time = tup[0]
# Unpacking each bootstrapped correlation function for easier analysis
unpacked_corr_func = {}
for i in range(max_time):
unpacked_corr_func[i] = []
for data in corr_data:
unpacked_corr_func[data[0] - 1].append(data[1])
# Working out the confidense intervals.
mean_corr_func = np.zeros(max_time)
lower = np.zeros(max_time)
upper = np.zeros(max_time)
for i in range(max_time):
mean_corr_func[i] = np.mean(unpacked_corr_func[i])
lower[i] = np.percentile(unpacked_corr_func[i], q=2.5)
upper[i] = np.percentile(unpacked_corr_func[i], q=97.5)
# When the first lower estimate hits zero, ensure that all supsequent data points are also zero.
zero_from = np.where(lower <= 0.0)[0][0]
lower[zero_from:] = 0
return mean_corr_func, lower, upper, auto_corr_time.mean(
), auto_corr_time.std()
def umbrella_PMF(x_kn,
data_path,
eq,
k_bias,
save_path,
temps_to_use='All',
save=True,
max_time=None):
"""
CURRENT FUNCTION USED TO COMPUTE SUBSTRUCTURE AND 1D PMF
x_kn is some list of coordiante values along which you want to compute free energies
We assume that x_kn is either an array where each row is a timecourse at a given condition, and the rows are in order of increasing reporter values (ex. temp or setpoint)
OR
that x_kn is a 1D array where a new trajectory starts every t values, and the trajectories are in order of increasing reporter values
You can also enter None, in whcih case x_kn is simply the native contacts
Alternatively you can enter x_kn as a string, for instnace 'rmsd', in whcih case the program extracts that variale from the data
IMPORTANT: YOU NEED TO MAKE SURE THAT THE POINTS IN X_KN CORRESPOND TO SAME TIMEPOINTS AS THE POINTS IN THE DATA FILE...IF IT DOESN'T, THEN
THE FUNCTION WILL TRY TO FIX IT BY SUBSAMPLING THE X_KN, BUT I DON'T TRUST THIS...
data_path tells you where the native contacts data is located
eq tells you how many steps you want to leave out initially while the simulations equilibrate
k_bias is the spring constant
save_path is where you want to save the results, for instance 'ADK_umbrella_multistart/Substructure_PMF.dat'
As a model for this, see pymbar/examples/umbrella-sampling-pmf/umbrella-sampling.py
May need to download this from github, not sure it's on home computer
By the way, on 3/17/20, added a parameter max_time, which is the last MC step to be used in equliibrium calculations
Typically, we use everything from eq till the end of the simulation (which is the case if max_time has its default value of None)
But if you set some numerical value for max_time, then we'll use somethign else
For instnace, if eq = 0 and max_time = 100000000, then we'll only use the first 100000000 MC timesteps to compute PMF
BUt if eq is set to, say, 150000000 and max_time is kept at its default value of None, then we use everything from 150000000 and beyond
to compute PMF
"""
print("# loading data...")
log_file_data, temperatures, setpoints, log_files, times, variables = load_data.load_log_data(
data_path)
energies_index = variables.index('energy')
energies = log_file_data[:, :, energies_index]
#
if 'natives' in variables:
natives_index = variables.index('natives')
natives = log_file_data[:, :, natives_index]
else: #assume no umbrella biasing
natives = np.zeros(np.shape(energies))
k_bias = 0
if type(x_kn) == str:
x_kn = log_file_data[:, :, variables.index(x_kn)]
elif np.shape(x_kn) == ():
x_kn = natives
setpoints = np.array(setpoints)
temperatures = np.array(temperatures)
n_conditions = np.shape(natives)[0]
x_kn = np.array(x_kn)
del log_file_data
if x_kn.ndim != 2:
x_kn = np.reshape(x_kn, (n_conditions, int(len(x_kn) / n_conditions)))
if temps_to_use != "All":
indices_to_use = [
t for t, temp in enumerate(temperatures) if temp in temps_to_use
]
natives = natives[indices_to_use, :]
energies = energies[indices_to_use, :]
x_kn = x_kn[indices_to_use, :]
n_conditions = len(indices_to_use)
temperatures = temperatures[indices_to_use]
setpoints = setpoints[indices_to_use]
sample_frequency = int(np.shape(natives)[1] / np.shape(x_kn)[1])
keep = np.arange(0, np.shape(natives)[1], sample_frequency)
natives = natives[:, keep]
energies = energies[:, keep]
times = np.array([times[t] for t in range(len(times)) if t in keep])
eq_index = np.where(times == eq)[0][0]
if max_time == None:
natives = natives[:, eq_index:]
energies = energies[:, eq_index:]
x_kn = x_kn[:, eq_index:]
else:
max_index = np.where(times == max_time)[0][0]
natives = natives[:, eq_index:max_index]
energies = energies[:, eq_index:max_index]
x_kn = x_kn[:, eq_index:max_index]
print(times[eq_index:max_index])
n_timepoints = np.shape(natives)[1]
print("# calculating potential...")
N_k = np.array([n_timepoints for k in range(n_conditions)], np.int32)
#u_kn=np.zeros()
u_kln = np.zeros((n_conditions, n_conditions, n_timepoints))
#ukln tells you the reduced potential energy (energy/kbT + spring cost) that
#point n from condition k would experience if it were to occur in some (other)
#condition l
for k in range(n_conditions):
for n in range(n_timepoints):
u_kln[k, :, n] = energies[k, n] / temperatures + k_bias * (
natives[k, n] - setpoints)**2
#Have to add in bias by hand since the energies term from log files does not include that bias!
print("# Computing normalizations...")
mbar = pymbar.MBAR(
u_kln, N_k
) #This initialization computes the log partition functions for all conditions (temperature/bias combinations)
#dF = mbar.getFreeEnergyDifferences()[0][0,:]
#In these previous steps, we compute the full trace (partition function) for all conditions (setpoint and temp combinations)...
#We will now compute the free energies (partial trace over only snapshots assigned to a state) under a DIFFERENT condition (which was not represented
#in the conditions whose normalizations we just calculated)--namely: the state in which you have no bias
unique_temperatures = np.unique(temperatures)
unique_x = np.unique(x_kn)
print('Computing state free energies...')
x_n = x_kn.flatten()
nbins = len(unique_x)
bin_n = np.array([np.where(unique_x == x)[0][0] for x in x_n])
free_energies = np.zeros((len(unique_temperatures), len(unique_x)))
uncertainties = np.zeros((len(unique_temperatures), len(unique_x)))
for t, temp in enumerate(unique_temperatures):
print("Computing free energy at T={}".format(temp))
u_n = energies.flatten() / unique_temperatures[
t] #reduced potential energy at temperature we care about
# we do NOT include bias in above formula because we want to compute the PMF specificlaly under the condition of no bias
#f_i, df_i = mbar.computePMF(u_n, bin_n, nbins, uncertainties='from-normalization')
f_i, df_i = mbar.computePMF(u_n,
bin_n,
nbins,
uncertainties='from-lowest')
#f_i, df_i = mbar.computePMF(u_n, bin_n, nbins, uncertainties='all-differences')
f_i = f_i - np.min(f_i) #set the lowest free energy to 0
#f_i=f_i+np.log(np.sum(np.exp(-f_i))) #normalize--this doesn't work well because you get overflow error
free_energies[t, :] = f_i
uncertainties[t, :] = df_i
"""
As for the uncertainties: Since I was not computing these for many of my previous proteins, I do not want to make a new variable
to avoid creating confusion with number of variables to be loaded by joblib
Rather, what I will do from now on is append the uncertainties to a second page of the free_energies array
Also, the uncertainties are scaled by sqrt(N/N_eff), where N is total nubmer of samples, and N_eff is effective number of uncorrelated samples
"""
#First, compute statistical inefficiency using all data
g = timeseries.statisticalInefficiencyMultiple(natives)
NNN = len(x_n)
N_eff = NNN / g
uncertainties = uncertainties * np.sqrt(NNN / N_eff)
free_energies = np.stack((free_energies, uncertainties), axis=2)
if save: joblib.dump([unique_x, free_energies, temperatures], save_path)
return unique_x, unique_temperatures, free_energies
psi_kt_replica = psi_kt.copy()
for iteration in range(niterations):
# Determine which snapshot indices are associated with this iteration
snapshot_indices = iteration*trajectory_segment_length + numpy.arange(0,trajectory_segment_length)
for k in range(K):
# Determine which replica generated the data from temperature k at this iteration
replica_index = replica_ik[iteration,k]
# Reconstruct portion of replica trajectory.
U_kt_replica[replica_index,snapshot_indices] = U_kt[k,snapshot_indices]
phi_kt_replica[replica_index,snapshot_indices] = phi_kt[k,snapshot_indices]
psi_kt_replica[replica_index,snapshot_indices] = psi_kt[k,snapshot_indices]
# Estimate the statistical inefficiency of the simulation by analyzing the timeseries of interest.
# We use the max of cos and sin of the phi and psi timeseries because they are periodic angles.
# The
print "Computing statistical inefficiencies..."
g_cosphi = timeseries.statisticalInefficiencyMultiple(numpy.cos(phi_kt_replica * numpy.pi / 180.0))
print "g_cos(phi) = %.1f" % g_cosphi
g_sinphi = timeseries.statisticalInefficiencyMultiple(numpy.sin(phi_kt_replica * numpy.pi / 180.0))
print "g_sin(phi) = %.1f" % g_sinphi
g_cospsi = timeseries.statisticalInefficiencyMultiple(numpy.cos(psi_kt_replica * numpy.pi / 180.0))
print "g_cos(psi) = %.1f" % g_cospsi
g_sinpsi = timeseries.statisticalInefficiencyMultiple(numpy.sin(psi_kt_replica * numpy.pi / 180.0))
print "g_sin(psi) = %.1f" % g_sinpsi
# Subsample data with maximum of all correlation times.
print "Subsampling data..."
g = numpy.max(numpy.array([g_cosphi, g_sinphi, g_cospsi, g_sinpsi]))
indices = timeseries.subsampleCorrelatedData(U_kt[k,:], g = g)
print "Using g = %.1f to obtain %d uncorrelated samples per temperature" % (g, len(indices))
N_max = int(numpy.ceil(T / g)) # max number of samples per temperature
U_kn = numpy.zeros([K, N_max], numpy.float64)
phi_kn = numpy.zeros([K, N_max], numpy.float64)
K = 10
if __name__ == "__main__":
var = numpy.ones(N)
for replica in xrange(2, K + 1):
var = numpy.concatenate((var, numpy.ones(N)))
X = numpy.random.normal(numpy.zeros(K * N), var).reshape((K, N)) / 10.0
Y = numpy.random.normal(numpy.zeros(K * N), var).reshape((K, N))
# X=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))
# Y=numpy.random.normal(numpy.zeros(K*N), var).reshape((K,N))
# print "X.shape = "
# print X.shape
energy = 10 * (X**2) / 2.0 + (Y**2) / 2.0
print "statisticalInefficiencyMultiple(X)"
print timeseries.statisticalInefficiencyMultiple(X)
print "statisticalInefficiencyMultiple(X**2)"
print timeseries.statisticalInefficiencyMultiple(X**2)
print "statisticalInefficiencyMultiple(X[0,:]**2)"
print timeseries.statisticalInefficiencyMultiple(X[0, :]**2)
print "statisticalInefficiencyMultiple(X[0:2,:]**2)"
print timeseries.statisticalInefficiencyMultiple(X[0:2, :]**2)
print "statisticalInefficiencyMultiple(energy)"
print timeseries.statisticalInefficiencyMultiple(energy)
# Exit with success.
# TODO: Add some checks to test statistical inefficinecies are within normal expected range.
sys.exit(0)
pickle_file = open(data_pickle_fn, 'wb')
dump( (U_kn_correlated, A_ikn_correlated), pickle_file )
pickle_file.close()
print ""
#######################################################################
# Subsample {U,A}_kn_correlated to be uncorrelated #
#######################################################################
print "Subsampling to achieve uncorrelated data"
if stat_inefficiency == None:
print "(1 of 2) Calculating statistical inefficiency (i = ",
stdout.flush()
for d in range(N_CVs):
statnew = timeseries.statisticalInefficiencyMultiple(A_ikn_correlated[d])
stat_inefficiency = max([stat_inefficiency, statnew])
print stat_inefficiency, ")"
else:
print "(1 of 2) Using given statistical inefficiency (i =", str(stat_inefficiency) + ")"
indices = timeseries.subsampleCorrelatedData(U_kn_correlated[0,:], g = stat_inefficiency)
N_uncorrelated_samples = len(indices)
print "(2 of 2) Subsampling to achieve", N_uncorrelated_samples, "samples per replica"
U_kn = zeros([ N_replicas+N_output_temps,N_uncorrelated_samples], float32)
A_ikn = zeros([N_CVs,N_replicas+N_output_temps,N_uncorrelated_samples], float32)
for k in range(N_replicas):
U_kn[k] = U_kn_correlated[k][indices]
