# adumb (c47b2)

Adaptive Umbrella Sampling Module

Setting up of adaptive umbrella potentials. Currently supported types

of umbrella potentials are functions of dihedral angles and functions of the

potential energy of the system (energy sampling). The module also supports

umbrella potentials that are functions of arbitrary reaction coordinates

defined using the RXNCOR commands (see

WARNING: The module is still being developed and some details are likely

to change in future versions.

Please report problems to Christian Bartels at cb@brel.u-strasbg.fr

Please report problems with the interface to the RXNCOR commands

to Justin Spiriti at jspiriti@usf.edu and/or Arjan van der Vaart

at avandervaart@usf.edu.

REFERENCES:

C. Bartels & M. Karplus, J. Comp. Chem. 18 (1997) 1450-

C. Bartels & M. Karplus, J. Phys. Chem. 102 (1998) 865-

M. Schaefer, C. Bartels, & M. Karplus, J. Mol. Biol. (1998)

* Syntax | Syntax of the ADUMB commands

* Function | Purpose of each of the commands

* Examples | Usage examples of the ADUMB module

Setting up of adaptive umbrella potentials. Currently supported types

of umbrella potentials are functions of dihedral angles and functions of the

potential energy of the system (energy sampling). The module also supports

umbrella potentials that are functions of arbitrary reaction coordinates

defined using the RXNCOR commands (see

**»**umbrel ).WARNING: The module is still being developed and some details are likely

to change in future versions.

Please report problems to Christian Bartels at cb@brel.u-strasbg.fr

Please report problems with the interface to the RXNCOR commands

to Justin Spiriti at jspiriti@usf.edu and/or Arjan van der Vaart

at avandervaart@usf.edu.

REFERENCES:

C. Bartels & M. Karplus, J. Comp. Chem. 18 (1997) 1450-

C. Bartels & M. Karplus, J. Phys. Chem. 102 (1998) 865-

M. Schaefer, C. Bartels, & M. Karplus, J. Mol. Biol. (1998)

* Syntax | Syntax of the ADUMB commands

* Function | Purpose of each of the commands

* Examples | Usage examples of the ADUMB module

Top

Syntax

[SYNTAX ADUMB functions]

Syntax:

ADUMb CORR DIST UNIT int SELE...END SELE...END (atom selection x 2)

CORR RMSD COR1

COR2

CORR RMSD SETUp NATOms int NSTRuctures int

CORR RMSD UNT1 1 int UNT2 int (atom selection x 3) -

ORIEnt SYMMetry 4X(atom-spec) FOLD int

ADUMb DIHE NRES int TRIG int POLY int 4X(atom-spec)

ADUMb ENER NRES int TRIG int POLY int

MAXE real MINE real [MAXT real] [MINT real]

ADUMb INIT NSIM int [UPDA int] [EQUI int] [TEMP real]

[AGIN real] [NEXT int] [THRE real]

[UCUN int] [WUNI int] [RUNI int] [FREQ int]

[WCUN int] [RCUN int] [CPFR int] [MAXB real]

ADUMb PROB UCUN int [TEMP real] [PUNI int] [TUNI int]

ADUMb RXNCor NRES int TRIG int POLY int NAME name MIN real MAX real

ADUMb STON

ADUMb STOFf

where: atom-spec ::= { segid resid iupac }

{ resnumber iupac }

Syntax

[SYNTAX ADUMB functions]

Syntax:

ADUMb CORR DIST UNIT int SELE...END SELE...END (atom selection x 2)

CORR RMSD COR1

COR2

CORR RMSD SETUp NATOms int NSTRuctures int

CORR RMSD UNT1 1 int UNT2 int (atom selection x 3) -

ORIEnt SYMMetry 4X(atom-spec) FOLD int

ADUMb DIHE NRES int TRIG int POLY int 4X(atom-spec)

ADUMb ENER NRES int TRIG int POLY int

MAXE real MINE real [MAXT real] [MINT real]

ADUMb INIT NSIM int [UPDA int] [EQUI int] [TEMP real]

[AGIN real] [NEXT int] [THRE real]

[UCUN int] [WUNI int] [RUNI int] [FREQ int]

[WCUN int] [RCUN int] [CPFR int] [MAXB real]

ADUMb PROB UCUN int [TEMP real] [PUNI int] [TUNI int]

ADUMb RXNCor NRES int TRIG int POLY int NAME name MIN real MAX real

ADUMb STON

ADUMb STOFf

where: atom-spec ::= { segid resid iupac }

{ resnumber iupac }

Top

0. Introduction

The module provides commands to define degrees of freedom along which

adaptive umbrella potentials are applied in molecular dynamics

simulations. Statistics on the sampling of the degrees of freedom are recorded

during the md simulations and periodically used to update the umbrella

potential such that uniform sampling of the degrees of freedom can be

expected. Currently, dihedral angles and the potential energy are supported

as degrees of freedom.

If several degrees of freedom are defined, multidimensional adaptive

umbrella sampling is performed.

Two sorts of input/output files are used by the module. The "umbrella"

files contain the umbrella potentials that were used in the simulations

together with the statistics of the sampling of the bins during the

simulations. Based on this information the potential of mean force can be

calculated and the umbrella potential expected to lead to uniform sampling

can be determined. The second sort of files contains the values of the

umbrella coordinates (=degree of freedom for adaptive umbrella sampling)

for each time step in which coordinates were saved to the trajectory files.

The umbrella coordinates are normalized to the range 0 to 1, independent of

the degrees of freedom used. From the umbrella coordinates saved, weighting

factors can be calculated which are needed to calculate average properties of

the unbiased system.

The ADUMB DIHE and ADUMB RXNCOR options have been updated to work with domain

decomposition (see

1. ADUMb DIHE

Define a dihedral angle as degree of freedom for adaptive umbrella

sampling. To record the statistics the degree of freedom is partitioned

into NRES bins. The umbrella potentials are represented as a linear combination

of two times TRIG trigonometric functions and polynomial functions of degree

0 to POLY - 1. Repeating the command results in a multidimensional adaptive

umbrella potential.

The coordinates written to the umbrella coordinates file are normalized

to the range 0 to 1 with 0 corresponding to -180 degrees and 1 corresponding

to +180 degrees.

2. ADUMb ENER

Define the potential energy as degree of freedom for adaptive umbrella

sampling. NRES, TRIG and POLY have the same meaning as in ADUMb DIHE.

MINE and MAXE specify the potential energy range: Statistics on the sampling

are recorded in the range MINE-0.5*(MAXE-MINE) to MAXE+0.5*(MAXE-MINE). In

the range outside of MINE to MAXE the umbrella potential is kept constant

to prevent the system from leaving the range in which statistics are recorded.

MINT and MAXT (default values: 273 K and 1000 K, respectively) are minimal

and maximal temperatures to restrict sampling in the relevant temperature

range. To set up a system, get a rough estimate of the potential energy of the

system at the desired TMIN and TMAX (from short unbiased simulations at

TMIN and TMAX). Set EMIN and EMAX to the values determined minus/plus a

small tolerance, respectively.

The coordinates written to the umbrella coordinates file are normalized

to the range 0 to 1 with 0 corresponding to MINE-0.5*(MAXE-MINE) and 1

corresponding to MAXE+0.5*(MAXE-MINE).

3. ADUMb INIT

Defines or redefines the parameters for adaptive umbrella sampling and

initializes the umbrella potential. The umbrella potential is updated

every UPDAte steps. After each update, no statistics are recorded for

EQUI steps. For the remaining UPDA - EQUI steps, statistics on the sampling

of the umbrella coordinates are recorded and stored separately from previous

statistics and together with the umbrella potential active when recording the

statistics. NSIM separate statistics can be kept in memory. If the number of

updates performed in a run exceeds NSIM, the oldest statistics are discarded

to make space for the most recent statistics.

After each update the umbrella potential and the statistics are written

to standard output (the log file). The written table contains, from left

to right, the number of the bin, the number of integration time steps in

which the system was in the bin since the last update, the potential of mean

force calculated with the WHAM equations, the negative of the updated

umbrella potential (potential of mean force modified to restrict sampling if

necessary and fitted to the set of trigonometric and polynomial functions),

the total number of times the bin was visited in the entire simulation, and

the umbrella coordinates of the center of the bin.

The temperature TEMP should be set to the temperature used in

the simulations. It is used to calculate the umbrella potentials from

the sampling statistics and to restrict sampling if potential energy

sampling is performed.

Umbrella coordinates are written to unit UCUN. At each update,

the statistics are written to unit WUNI together with the umbrella potential

active when recording the statistics. Statistics from previous runs can

be read from unit RUNI. The statistics read must be from adaptive umbrella

sampling simulations with the same parameters as the present one, in

particular, the same degrees of freedom have to be used as umbrella

coordinates. If adaptive umbrella sampling of the potential energy is

used, umbrella potentials from runs at different temperatures can

be read by repeating the ADUMb INIT command with RUNI set to the unit

containing the statistics of each of the runs and TEMP set to the temperature

of the run.

To define the umbrella potential of bins for which no statistics

have been acquired so far, the umbrella potential has to be extrapolated.

In the current implementation (might change in future implementations),

the umbrella potential of the bins that were not sampled is set to

the same value (ext-cons). To determine ext-cons, the potential of the bins

that were sampled is linearly extrapolated for NEXT bins, and the maximal

value (max-extrapolated) of the linearly extrapolated potentials is

determined. Then, the minimal value (min-sampled) of the potentials of the

bins that were sampled is determined and ext-cons is set to min-sampled

or max-extrapolated whatever value is smaller.

A few statistics that differ significantly from the rest of the

statistics can be due to problems with the convergence caused by the

extrapolation or due to the occurrence of rare events. In the former case,

outliers should occur only in the first few simulations and it is advantageous

to eliminate them. By default, the module eliminates statistics that

differ from the averaged statistics by THRE times the average deviation. If

one wants to prevent statistics from being eliminated THRE has to be set to

a value larger than NSIM. At each update, the deviations of the statistics

from the averaged statistics is printed to standard output (log file), e.g.,

0 Deviation of simulation 1 : 0.955

0 Deviation of simulation 2 : 0.513E-01

0 Deviation of simulation 3 : 0.787E-01

0 Deviation of simulation 4 : 0.292

0 Deviation of simulation 5 : 0.170

0 Deviation of simulation 6 : 0.201

0 Deviation of simulation 7 : 0.933

0 Deviation of simulation 8 : 0.208

0 Deviation of simulation 9 : 0.270

0 Deviation of simulation 10 : 0.131

0 Deviation of simulation 11 : 0.394

0 Deviation of simulation 12 : 1.52

0 Deviation of simulation 13 : 0.969

0 Deviation of simulation 14 : 0.502

0 Deviation of simulation 15 : 1.47

0 Deviation of simulation 16 : 2.97

-1 Deviation of simulation 17 : 210.

0 Deviation of simulation 18 : 0.695E-01

0 Deviation of simulation 19 : 0.160

0 Deviation of simulation 20 : 0.450

The 0 or -1 on each line indicates whether the statistics of a particular

simulation are used (0) or were discarded (-1) based on the THRE criterion.

For complex systems, there might exist no umbrella potential that

enables the system to diffuse rapidly along the umbrella coordinate. In

such cases it has been found to be advantageous to give a higher weight

to the most recent statistics. This is implemented using the AGINg factor.

For an umbrella potential calculated from n statistics, the i'th statistics

(i=1,2,..,n) are weighted by AGINg**(n-i).

The FREQ keyword specifies the frequency with which the dynamics

trajectories are sampled for compilation of the umbrella potential

statistics. FREQ 2 for example means that every other point along the

trajectory is sampled.

WCUNit and RCUNit specify the units to which the accumulators for the

correlated structural variables are to be written and read, for the purposes

of restarting trajectories. The accumulators, along with the updated

average results, will be written every CPFRequency updates of the umbrella

potential (see also ADUMb CORR). If WCUNit and RCUNit are omitted, no

writing of the accumulator statistics will be done.

A MAXBias option has been added to limit the magnitude of the umbrella

potential. This works by applying the formula

U_bias(q) = -beta^-1 * ln(exp(-beta*F(q)) + exp(-beta*U_max))

where F(q) is the free energy surface and U_max is the maximum bias. This

is primarily intended for use with the roll angle reaction coordinate, where a

cap on the biasing potential is needed to prevent numerical instabilities (see

Spiriti and van der Vaart, JCTC 8, 2145 (2012)).

4. ADUMb PROB

Average properties of the unbiased system can be obtained by weighting

the conformations of an adaptive umbrella sampling run by appropriate

factors. The ADUMb PROB command calculates these weighting factors from

the umbrella coordinates read from unit UCUN and writes them to unit PUNI.

For the command to work the umbrella potentials and statistics from the

run must have been read with the ADUMb INIT command. If the potential

energy was used as umbrella coordinate, the TEMP specifies the temperature

at which properties of the unbiased system should be calculated.

5. ADUMb RXNCor

Use a coordinate that has been previously defined using the RXNCOR DEFIne

and RXNCOR SET commands (see

coordinate for adaptive umbrella sampling. NRES, TRIG and POLY have the

same meaning as in ADUMB DIHE. The NAME option specifies the name of the

coordinate to be used. The MIN and MAX options specify the minimum and

maximum values of the coordinate; if the coordinate exceeds the values

specified during the simulation an error will be produced. This command

may be used to perform adaptive umbrella sampling on the roll angle reaction

coordinate (see

6. ADUMb STON

ADUMb STOFf

By default statistics on the sampling of the umbrella coordinates are

recorded in each call to the energy routines. The ADUMb STOFf command

prevents that statistics are recorded. This might be useful when doing

a minimization or running a md simulation with an umbrella potential

that should not change during the simulation.

7. ADUMb CORRelations

The CORRelations keyword allows for the running calculation of the

average values of specified structural variables over the course of the

trajectores as a function of the reaction coordinates. It is intended

as a tool for examining correlations between the reaction coordinates

and various other structural variables in the system. It is currently

implemented for interatomic distances and substructure rmsd's. The average

values for the specified variables (distances or rmsd's) are written to

a file (or to standard output) every CPFR times the umbrella potential is

updated, where CPFR is a keyword specified in the UMBR INIT command.

Correlated Distances:

*********************

The UMBR CORR DIST command sets up the calculation of an average inter-

atomic distance, between atoms specified with a double atom selection.

Only one atom may be specified for each atom selection. The UMBR CORR DIST

command must be given once for each interatomic distance to be calcu-

lated. The UNIT keyword is followed by the unit number to which the

results are to be written. If no unit number is specified, the results

for the correlated distances will be written to standard output. If a

unit number is specified for any distance, they must be specified for

all distances. The average distance results will be written every

CPFRequency updates of the umbrella potential (see ADUMb INIT).

Up to 100 distances can be specified.

EXAMPLE:

umbrella corr dist unit 17 sele atom1 end -

sele atom2 end

This will result in the calculation of the running average of the

distance between atom1 and atom2. (The selection of less than or

greater than exactly 2 atoms will result in an error.)

The output is formatted as follows:

Average vals of distance fr 17 to 6 at step 500

2 1 -1.00000000 7.25430918

2 2 -1.00000000 6.89725628

2 3 -1.00000000 6.69046274

2 4 6.38194491 6.41586493

2 5 5.92699253 5.84622204

The first line describes the variable

The first column gives the assigned number of the distance variable.

The second column gives the position of the reaction coordinate

(same as in free energy output). The third column gives the average

value of the distance over the last trajectory. The fourth column gives

the cumulative average over all trajectories. A "-1" value indicates

that the reaction coordinate position has not been visited.

Correlated Substructure RMSD's:

*******************************

The UMBR CORR RMSD commands allow for the calculation of the running

average of the rmsd's, as a function of the reaction coordinates,

for specified parts of the system relative to 2 reference structures.

UMBR CORR RMSD COR1 !saves the current coords as reference structure #1.

UMBR CORR RMSD COR2 !saves the current coords as reference structure #2.

UMBR CORR RMSD SETUp NATOms int NSTRuctures int WCUNit int RCUNit int

This command gives the memory specifications, where NATOms is the

total number of atoms that will be selected for all UMBR CORR RMSD

calculations, and NSTRuctures is the number of sets of substructures

for which RMSD calculations are to be carried out. WCUNit and RCUNit

specify the units to which the accumulators are to be written/read for

the purposes of restarting trajectories. The accumulator values will

be written every CPFRequency updates of the umbrella potential (see also

ADUMb INIT).

The above three commands must be invoked prior to the last set of commands

(UMBR CORR RMSD SUBStructure), which specifies the atoms involved in

the rmsd calculations:

UMBR CORR RMSD SUBStructure UNT1 1 int UNT2 int (atom selection x 3) -

ORIEnt SYMMetry 4X(atom-spec) FOLD int

UNT1 and UNT2 are the unit numbers for the output (average rmsd's

relative to reference structures 1 and 2, respectively). If no unit

numbers are specified, the results are written to standard output. Unit

numbers must be specified for either all UMBR CORR RMSD SUBS commands or

none of them (i.e. either all results are written to files or all are

written to standard output).

The three atom selections specify the following (in order):

1) the atoms whose rmsd is to be calculated

2) the atoms relative to which a reorientation of the

system is to take place prior to calculation of the rmsd

and 3) the atoms involved in a symmetry operation that will be

done prior to the calculation of the rmsd.

The ORIEnt keyword invokes a reorientation of the system.

The SYMMetry keyword invokes the symmetry operation, which is a dihedral

angle rotation specified by 4 atoms. The FOLD keyword specifies the

multiplicity of the symmetry. The final rmsd will be the lowest one

calculated for any of the symmetric positions. (Only 1 symmetry oper-

ation is allowed per rmsd calculation, currently). Since the positions

of atoms in this (3rd) selection will be initialized and rebuilt according

to the internal coordinates of the initialized fragment and the cartesian

coordinates of the rest of the structure, care must be taken in the

selection so as to ensure the initialized fragment is not too large.

If the ORIEnt keyword is specified and only one atom selection is given,

the reorientation (as well as the rmsd calculation) will be done relative

to this selection. If only one or two atom selections are given, no

symmetry operation will occur (irrespective of the presence or absence of

reorientation).

The UMBR CORR RMSD SUBStructure command must be invoked once for each set of

rmsd substructure calculations to be done during the dynamics.

Example

UMBRELLA CORR RMSD SUBS UNT1 27 UNT2 28 SELE (phe residue) END -

SELE (phe backbone) END -

SELE (phe sidechain) END -

ORIE SYMM 2 CA 2 CB 2 CG 2 CD1 FOLD 2

This command specifies that the rmsd will be calculated relative to

the "phe residue" atoms. Reorientation will be done relative to the

"phe backbone" atoms prior to the rmsd calculation. A 2-fold symmetry

operation will be carried out involving the "phe sidechain" atoms and

a rotation about the dihedral defined by 2 CA 2 CB 2 CG 2 CD1. The

rmsd relative to reference structure 1 will be written to unit 27 and

that relative to reference structure 2 will be written to unit 28.

Example

UMBRELLA CORR RMSD SUBS UNT1 27 UNT2 28 SELE (phe residue) END -

SELE (phe backbone) END -

ORIE

This will result in the same calculation as above, absent the symmetry

operation.

The output is formatted as follows:

Average RMSDs from Ref #1 for set 35 at step 500000

35 1 -1.00000000 1.11056063

35 2 -1.00000000 1.09866706

35 3 -1.00000000 1.05065449

35 4 -1.00000000 1.09327534

35 5 -1.00000000 1.07153876

35 6 -1.00000000 -1.00000000

35 7 -1.00000000 -1.00000000

The first column gives the number of the substructure (numbered

serially from 1 with each UMBR CORR RMSD command). The second column

gives the reaction coordinate gridpoint. The third column gives

the average rmsd over the last trajectory. The fourth column gives

the average rmsd over all trajectories.

NOTE that specification of any correlated variables must be followed

by an UMBRella INIT command, prior to the start of dynamics.

In addition, the specification of any correlated variables will reset

the umbrella potential, causing the previously accumulated statistics

to be discarded. This is to ensure exact correspondence between the

statistical ensembles that are sampled for the free energy surface

and the structural variables.

In adaptive umbrella sampling without structural correlations,

trajectories (sampling runs between updates) that deviate more than a

specified tolerance from the average trajectory are removed from the

statistics. This filtering feature is disabled when structural

correlations are invoked, due to the large memory requirements.

The "aging" option, whereby older trajectories may be weighted by

the user less heavily than more recent trajectories, is preserved

for the free energy surfaces when structural correlations are invoked,

but the feature is not implemented for the structural correlations,

themselves, again because of large memory requirements. Hence aging

the trajectories may result in free energy surfaces and structural

correlations that are derived from different statistical distributions.

0. Introduction

The module provides commands to define degrees of freedom along which

adaptive umbrella potentials are applied in molecular dynamics

simulations. Statistics on the sampling of the degrees of freedom are recorded

during the md simulations and periodically used to update the umbrella

potential such that uniform sampling of the degrees of freedom can be

expected. Currently, dihedral angles and the potential energy are supported

as degrees of freedom.

If several degrees of freedom are defined, multidimensional adaptive

umbrella sampling is performed.

Two sorts of input/output files are used by the module. The "umbrella"

files contain the umbrella potentials that were used in the simulations

together with the statistics of the sampling of the bins during the

simulations. Based on this information the potential of mean force can be

calculated and the umbrella potential expected to lead to uniform sampling

can be determined. The second sort of files contains the values of the

umbrella coordinates (=degree of freedom for adaptive umbrella sampling)

for each time step in which coordinates were saved to the trajectory files.

The umbrella coordinates are normalized to the range 0 to 1, independent of

the degrees of freedom used. From the umbrella coordinates saved, weighting

factors can be calculated which are needed to calculate average properties of

the unbiased system.

The ADUMB DIHE and ADUMB RXNCOR options have been updated to work with domain

decomposition (see

**»**umbrel ).1. ADUMb DIHE

Define a dihedral angle as degree of freedom for adaptive umbrella

sampling. To record the statistics the degree of freedom is partitioned

into NRES bins. The umbrella potentials are represented as a linear combination

of two times TRIG trigonometric functions and polynomial functions of degree

0 to POLY - 1. Repeating the command results in a multidimensional adaptive

umbrella potential.

The coordinates written to the umbrella coordinates file are normalized

to the range 0 to 1 with 0 corresponding to -180 degrees and 1 corresponding

to +180 degrees.

2. ADUMb ENER

Define the potential energy as degree of freedom for adaptive umbrella

sampling. NRES, TRIG and POLY have the same meaning as in ADUMb DIHE.

MINE and MAXE specify the potential energy range: Statistics on the sampling

are recorded in the range MINE-0.5*(MAXE-MINE) to MAXE+0.5*(MAXE-MINE). In

the range outside of MINE to MAXE the umbrella potential is kept constant

to prevent the system from leaving the range in which statistics are recorded.

MINT and MAXT (default values: 273 K and 1000 K, respectively) are minimal

and maximal temperatures to restrict sampling in the relevant temperature

range. To set up a system, get a rough estimate of the potential energy of the

system at the desired TMIN and TMAX (from short unbiased simulations at

TMIN and TMAX). Set EMIN and EMAX to the values determined minus/plus a

small tolerance, respectively.

The coordinates written to the umbrella coordinates file are normalized

to the range 0 to 1 with 0 corresponding to MINE-0.5*(MAXE-MINE) and 1

corresponding to MAXE+0.5*(MAXE-MINE).

3. ADUMb INIT

Defines or redefines the parameters for adaptive umbrella sampling and

initializes the umbrella potential. The umbrella potential is updated

every UPDAte steps. After each update, no statistics are recorded for

EQUI steps. For the remaining UPDA - EQUI steps, statistics on the sampling

of the umbrella coordinates are recorded and stored separately from previous

statistics and together with the umbrella potential active when recording the

statistics. NSIM separate statistics can be kept in memory. If the number of

updates performed in a run exceeds NSIM, the oldest statistics are discarded

to make space for the most recent statistics.

After each update the umbrella potential and the statistics are written

to standard output (the log file). The written table contains, from left

to right, the number of the bin, the number of integration time steps in

which the system was in the bin since the last update, the potential of mean

force calculated with the WHAM equations, the negative of the updated

umbrella potential (potential of mean force modified to restrict sampling if

necessary and fitted to the set of trigonometric and polynomial functions),

the total number of times the bin was visited in the entire simulation, and

the umbrella coordinates of the center of the bin.

The temperature TEMP should be set to the temperature used in

the simulations. It is used to calculate the umbrella potentials from

the sampling statistics and to restrict sampling if potential energy

sampling is performed.

Umbrella coordinates are written to unit UCUN. At each update,

the statistics are written to unit WUNI together with the umbrella potential

active when recording the statistics. Statistics from previous runs can

be read from unit RUNI. The statistics read must be from adaptive umbrella

sampling simulations with the same parameters as the present one, in

particular, the same degrees of freedom have to be used as umbrella

coordinates. If adaptive umbrella sampling of the potential energy is

used, umbrella potentials from runs at different temperatures can

be read by repeating the ADUMb INIT command with RUNI set to the unit

containing the statistics of each of the runs and TEMP set to the temperature

of the run.

To define the umbrella potential of bins for which no statistics

have been acquired so far, the umbrella potential has to be extrapolated.

In the current implementation (might change in future implementations),

the umbrella potential of the bins that were not sampled is set to

the same value (ext-cons). To determine ext-cons, the potential of the bins

that were sampled is linearly extrapolated for NEXT bins, and the maximal

value (max-extrapolated) of the linearly extrapolated potentials is

determined. Then, the minimal value (min-sampled) of the potentials of the

bins that were sampled is determined and ext-cons is set to min-sampled

or max-extrapolated whatever value is smaller.

A few statistics that differ significantly from the rest of the

statistics can be due to problems with the convergence caused by the

extrapolation or due to the occurrence of rare events. In the former case,

outliers should occur only in the first few simulations and it is advantageous

to eliminate them. By default, the module eliminates statistics that

differ from the averaged statistics by THRE times the average deviation. If

one wants to prevent statistics from being eliminated THRE has to be set to

a value larger than NSIM. At each update, the deviations of the statistics

from the averaged statistics is printed to standard output (log file), e.g.,

0 Deviation of simulation 1 : 0.955

0 Deviation of simulation 2 : 0.513E-01

0 Deviation of simulation 3 : 0.787E-01

0 Deviation of simulation 4 : 0.292

0 Deviation of simulation 5 : 0.170

0 Deviation of simulation 6 : 0.201

0 Deviation of simulation 7 : 0.933

0 Deviation of simulation 8 : 0.208

0 Deviation of simulation 9 : 0.270

0 Deviation of simulation 10 : 0.131

0 Deviation of simulation 11 : 0.394

0 Deviation of simulation 12 : 1.52

0 Deviation of simulation 13 : 0.969

0 Deviation of simulation 14 : 0.502

0 Deviation of simulation 15 : 1.47

0 Deviation of simulation 16 : 2.97

-1 Deviation of simulation 17 : 210.

0 Deviation of simulation 18 : 0.695E-01

0 Deviation of simulation 19 : 0.160

0 Deviation of simulation 20 : 0.450

The 0 or -1 on each line indicates whether the statistics of a particular

simulation are used (0) or were discarded (-1) based on the THRE criterion.

For complex systems, there might exist no umbrella potential that

enables the system to diffuse rapidly along the umbrella coordinate. In

such cases it has been found to be advantageous to give a higher weight

to the most recent statistics. This is implemented using the AGINg factor.

For an umbrella potential calculated from n statistics, the i'th statistics

(i=1,2,..,n) are weighted by AGINg**(n-i).

The FREQ keyword specifies the frequency with which the dynamics

trajectories are sampled for compilation of the umbrella potential

statistics. FREQ 2 for example means that every other point along the

trajectory is sampled.

WCUNit and RCUNit specify the units to which the accumulators for the

correlated structural variables are to be written and read, for the purposes

of restarting trajectories. The accumulators, along with the updated

average results, will be written every CPFRequency updates of the umbrella

potential (see also ADUMb CORR). If WCUNit and RCUNit are omitted, no

writing of the accumulator statistics will be done.

A MAXBias option has been added to limit the magnitude of the umbrella

potential. This works by applying the formula

U_bias(q) = -beta^-1 * ln(exp(-beta*F(q)) + exp(-beta*U_max))

where F(q) is the free energy surface and U_max is the maximum bias. This

is primarily intended for use with the roll angle reaction coordinate, where a

cap on the biasing potential is needed to prevent numerical instabilities (see

Spiriti and van der Vaart, JCTC 8, 2145 (2012)).

4. ADUMb PROB

Average properties of the unbiased system can be obtained by weighting

the conformations of an adaptive umbrella sampling run by appropriate

factors. The ADUMb PROB command calculates these weighting factors from

the umbrella coordinates read from unit UCUN and writes them to unit PUNI.

For the command to work the umbrella potentials and statistics from the

run must have been read with the ADUMb INIT command. If the potential

energy was used as umbrella coordinate, the TEMP specifies the temperature

at which properties of the unbiased system should be calculated.

5. ADUMb RXNCor

Use a coordinate that has been previously defined using the RXNCOR DEFIne

and RXNCOR SET commands (see

**»**umbrel ) as a reactioncoordinate for adaptive umbrella sampling. NRES, TRIG and POLY have the

same meaning as in ADUMB DIHE. The NAME option specifies the name of the

coordinate to be used. The MIN and MAX options specify the minimum and

maximum values of the coordinate; if the coordinate exceeds the values

specified during the simulation an error will be produced. This command

may be used to perform adaptive umbrella sampling on the roll angle reaction

coordinate (see

**»**umbrel )6. ADUMb STON

ADUMb STOFf

By default statistics on the sampling of the umbrella coordinates are

recorded in each call to the energy routines. The ADUMb STOFf command

prevents that statistics are recorded. This might be useful when doing

a minimization or running a md simulation with an umbrella potential

that should not change during the simulation.

7. ADUMb CORRelations

The CORRelations keyword allows for the running calculation of the

average values of specified structural variables over the course of the

trajectores as a function of the reaction coordinates. It is intended

as a tool for examining correlations between the reaction coordinates

and various other structural variables in the system. It is currently

implemented for interatomic distances and substructure rmsd's. The average

values for the specified variables (distances or rmsd's) are written to

a file (or to standard output) every CPFR times the umbrella potential is

updated, where CPFR is a keyword specified in the UMBR INIT command.

Correlated Distances:

*********************

The UMBR CORR DIST command sets up the calculation of an average inter-

atomic distance, between atoms specified with a double atom selection.

Only one atom may be specified for each atom selection. The UMBR CORR DIST

command must be given once for each interatomic distance to be calcu-

lated. The UNIT keyword is followed by the unit number to which the

results are to be written. If no unit number is specified, the results

for the correlated distances will be written to standard output. If a

unit number is specified for any distance, they must be specified for

all distances. The average distance results will be written every

CPFRequency updates of the umbrella potential (see ADUMb INIT).

Up to 100 distances can be specified.

EXAMPLE:

umbrella corr dist unit 17 sele atom1 end -

sele atom2 end

This will result in the calculation of the running average of the

distance between atom1 and atom2. (The selection of less than or

greater than exactly 2 atoms will result in an error.)

The output is formatted as follows:

Average vals of distance fr 17 to 6 at step 500

2 1 -1.00000000 7.25430918

2 2 -1.00000000 6.89725628

2 3 -1.00000000 6.69046274

2 4 6.38194491 6.41586493

2 5 5.92699253 5.84622204

The first line describes the variable

The first column gives the assigned number of the distance variable.

The second column gives the position of the reaction coordinate

(same as in free energy output). The third column gives the average

value of the distance over the last trajectory. The fourth column gives

the cumulative average over all trajectories. A "-1" value indicates

that the reaction coordinate position has not been visited.

Correlated Substructure RMSD's:

*******************************

The UMBR CORR RMSD commands allow for the calculation of the running

average of the rmsd's, as a function of the reaction coordinates,

for specified parts of the system relative to 2 reference structures.

UMBR CORR RMSD COR1 !saves the current coords as reference structure #1.

UMBR CORR RMSD COR2 !saves the current coords as reference structure #2.

UMBR CORR RMSD SETUp NATOms int NSTRuctures int WCUNit int RCUNit int

This command gives the memory specifications, where NATOms is the

total number of atoms that will be selected for all UMBR CORR RMSD

calculations, and NSTRuctures is the number of sets of substructures

for which RMSD calculations are to be carried out. WCUNit and RCUNit

specify the units to which the accumulators are to be written/read for

the purposes of restarting trajectories. The accumulator values will

be written every CPFRequency updates of the umbrella potential (see also

ADUMb INIT).

The above three commands must be invoked prior to the last set of commands

(UMBR CORR RMSD SUBStructure), which specifies the atoms involved in

the rmsd calculations:

UMBR CORR RMSD SUBStructure UNT1 1 int UNT2 int (atom selection x 3) -

ORIEnt SYMMetry 4X(atom-spec) FOLD int

UNT1 and UNT2 are the unit numbers for the output (average rmsd's

relative to reference structures 1 and 2, respectively). If no unit

numbers are specified, the results are written to standard output. Unit

numbers must be specified for either all UMBR CORR RMSD SUBS commands or

none of them (i.e. either all results are written to files or all are

written to standard output).

The three atom selections specify the following (in order):

1) the atoms whose rmsd is to be calculated

2) the atoms relative to which a reorientation of the

system is to take place prior to calculation of the rmsd

and 3) the atoms involved in a symmetry operation that will be

done prior to the calculation of the rmsd.

The ORIEnt keyword invokes a reorientation of the system.

The SYMMetry keyword invokes the symmetry operation, which is a dihedral

angle rotation specified by 4 atoms. The FOLD keyword specifies the

multiplicity of the symmetry. The final rmsd will be the lowest one

calculated for any of the symmetric positions. (Only 1 symmetry oper-

ation is allowed per rmsd calculation, currently). Since the positions

of atoms in this (3rd) selection will be initialized and rebuilt according

to the internal coordinates of the initialized fragment and the cartesian

coordinates of the rest of the structure, care must be taken in the

selection so as to ensure the initialized fragment is not too large.

If the ORIEnt keyword is specified and only one atom selection is given,

the reorientation (as well as the rmsd calculation) will be done relative

to this selection. If only one or two atom selections are given, no

symmetry operation will occur (irrespective of the presence or absence of

reorientation).

The UMBR CORR RMSD SUBStructure command must be invoked once for each set of

rmsd substructure calculations to be done during the dynamics.

Example

UMBRELLA CORR RMSD SUBS UNT1 27 UNT2 28 SELE (phe residue) END -

SELE (phe backbone) END -

SELE (phe sidechain) END -

ORIE SYMM 2 CA 2 CB 2 CG 2 CD1 FOLD 2

This command specifies that the rmsd will be calculated relative to

the "phe residue" atoms. Reorientation will be done relative to the

"phe backbone" atoms prior to the rmsd calculation. A 2-fold symmetry

operation will be carried out involving the "phe sidechain" atoms and

a rotation about the dihedral defined by 2 CA 2 CB 2 CG 2 CD1. The

rmsd relative to reference structure 1 will be written to unit 27 and

that relative to reference structure 2 will be written to unit 28.

Example

UMBRELLA CORR RMSD SUBS UNT1 27 UNT2 28 SELE (phe residue) END -

SELE (phe backbone) END -

ORIE

This will result in the same calculation as above, absent the symmetry

operation.

The output is formatted as follows:

Average RMSDs from Ref #1 for set 35 at step 500000

35 1 -1.00000000 1.11056063

35 2 -1.00000000 1.09866706

35 3 -1.00000000 1.05065449

35 4 -1.00000000 1.09327534

35 5 -1.00000000 1.07153876

35 6 -1.00000000 -1.00000000

35 7 -1.00000000 -1.00000000

The first column gives the number of the substructure (numbered

serially from 1 with each UMBR CORR RMSD command). The second column

gives the reaction coordinate gridpoint. The third column gives

the average rmsd over the last trajectory. The fourth column gives

the average rmsd over all trajectories.

NOTE that specification of any correlated variables must be followed

by an UMBRella INIT command, prior to the start of dynamics.

In addition, the specification of any correlated variables will reset

the umbrella potential, causing the previously accumulated statistics

to be discarded. This is to ensure exact correspondence between the

statistical ensembles that are sampled for the free energy surface

and the structural variables.

In adaptive umbrella sampling without structural correlations,

trajectories (sampling runs between updates) that deviate more than a

specified tolerance from the average trajectory are removed from the

statistics. This filtering feature is disabled when structural

correlations are invoked, due to the large memory requirements.

The "aging" option, whereby older trajectories may be weighted by

the user less heavily than more recent trajectories, is preserved

for the free energy surfaces when structural correlations are invoked,

but the feature is not implemented for the structural correlations,

themselves, again because of large memory requirements. Hence aging

the trajectories may result in free energy surfaces and structural

correlations that are derived from different statistical distributions.

Top

Examples

This examples are meant to be a partial guide in setting up

an input file for ADUMB. There are three test files, adumb-phichi.inp,

adumb-enum.inp and ace2.inp.

Example (1)

-----------

Set up and run an adaptive umbrella sampling simulation using two dihedral

angles as umbrella coordinates.

! define the phi and chi1 dihedral angle as the two umbrella coordinates

umbrella dihe nresol 36 trig 6 poly 1 pept 1 N pept 1 CA pept 1 CB pept 1 OG1

umbrella dihe nresol 36 trig 6 poly 1 pept 1 CY pept 1 N pept 1 CA pept 1 C

umbrella init nsim 100 update 10000 equi 1000 thresh 10 temp 300 -

ucun 10 wuni 11

! perform adaptive umbrella sampling md simulation

dynamics nose tref 300 qref 20 start -

nstep 20000 timestep 0.001 -

ihbfrq 0 inbfrq 10 ilbfrq 5 -

iseed 12 -

nprint 1000 iprfreq 1000 -

isvfrq 1000 iunwrite -1 iunread -1 -

wmin 1.2

Example(2)

----------

Set up and run an adaptive umbrella sampling simulation using the potential

energy as umbrella coordinate (=energy sampling, multicanonical simulation,

entropic sampling).

! set up umbrella; the range of relevant potential energies is assumed to

! extend form -50 kcal/mol to 100 kcal/mol.

umbrella ener nresol 200 trig 20 poly 5 mine -50 maxe 100.0 mint 280 maxt 2000

open write formatted unit 9 name @9enum.umb

open write formatted unit 10 name @9enum.uco

open write unformatted unit 11 name @9enum.cor

umbrella init nsim 100 update 10000 equi 1000 temp 1000 thres 100 -

wuni 9 ucun 10

! energy sampling simulation

dynamics langevin start -

nstep 50000 timestep 0.001 -

inbfrq 10 ilbfrq 10 rbuffer 0.0 tbath 1000 -

iseed 12 -

nprint 1000 iprfreq 1000 -

isvfrq 1000 iunwrite -1 iunread -1 -

nsavc 100 iuncrd 11 -

wmin 1.2

Example(3)

----------

Determine the weighting factors to calculate properties of the

unbiased system.

! define the umbrella coordinates

umbrella ener nresol 200 trig 20 poly 5 mine -50 maxe 100.0 mint 280 maxt 2000

open read formatted unit 10 name ../scr/@n.umb

umbrella init nsim 100 update 10000 equi 1000 runi 10 temp 1000 thres 200

! translate umbrella coordinates into probability factors at 300K

open read formatted unit 11 name ../scr/@n.uco

open write formatted unit 12 name ../scr/@nT300K.pfa

umbrella prob ucun 11 puni 12 temp 300

! translate umbrella coordinates into probability factors at 1000K

open read formatted unit 11 name ../scr/@n.uco

open write formatted unit 12 name ../scr/@nT1000K.pfa

umbrella prob ucun 11 puni 12 temp 1000

Example(4)

----------

Set up and run an adaptive umbrella sampling simulation using an interatomic

distance as a reaction coordinate.

Examples

This examples are meant to be a partial guide in setting up

an input file for ADUMB. There are three test files, adumb-phichi.inp,

adumb-enum.inp and ace2.inp.

Example (1)

-----------

Set up and run an adaptive umbrella sampling simulation using two dihedral

angles as umbrella coordinates.

! define the phi and chi1 dihedral angle as the two umbrella coordinates

umbrella dihe nresol 36 trig 6 poly 1 pept 1 N pept 1 CA pept 1 CB pept 1 OG1

umbrella dihe nresol 36 trig 6 poly 1 pept 1 CY pept 1 N pept 1 CA pept 1 C

umbrella init nsim 100 update 10000 equi 1000 thresh 10 temp 300 -

ucun 10 wuni 11

! perform adaptive umbrella sampling md simulation

dynamics nose tref 300 qref 20 start -

nstep 20000 timestep 0.001 -

ihbfrq 0 inbfrq 10 ilbfrq 5 -

iseed 12 -

nprint 1000 iprfreq 1000 -

isvfrq 1000 iunwrite -1 iunread -1 -

wmin 1.2

Example(2)

----------

Set up and run an adaptive umbrella sampling simulation using the potential

energy as umbrella coordinate (=energy sampling, multicanonical simulation,

entropic sampling).

! set up umbrella; the range of relevant potential energies is assumed to

! extend form -50 kcal/mol to 100 kcal/mol.

umbrella ener nresol 200 trig 20 poly 5 mine -50 maxe 100.0 mint 280 maxt 2000

open write formatted unit 9 name @9enum.umb

open write formatted unit 10 name @9enum.uco

open write unformatted unit 11 name @9enum.cor

umbrella init nsim 100 update 10000 equi 1000 temp 1000 thres 100 -

wuni 9 ucun 10

! energy sampling simulation

dynamics langevin start -

nstep 50000 timestep 0.001 -

inbfrq 10 ilbfrq 10 rbuffer 0.0 tbath 1000 -

iseed 12 -

nprint 1000 iprfreq 1000 -

isvfrq 1000 iunwrite -1 iunread -1 -

nsavc 100 iuncrd 11 -

wmin 1.2

Example(3)

----------

Determine the weighting factors to calculate properties of the

unbiased system.

! define the umbrella coordinates

umbrella ener nresol 200 trig 20 poly 5 mine -50 maxe 100.0 mint 280 maxt 2000

open read formatted unit 10 name ../scr/@n.umb

umbrella init nsim 100 update 10000 equi 1000 runi 10 temp 1000 thres 200

! translate umbrella coordinates into probability factors at 300K

open read formatted unit 11 name ../scr/@n.uco

open write formatted unit 12 name ../scr/@nT300K.pfa

umbrella prob ucun 11 puni 12 temp 300

! translate umbrella coordinates into probability factors at 1000K

open read formatted unit 11 name ../scr/@n.uco

open write formatted unit 12 name ../scr/@nT1000K.pfa

umbrella prob ucun 11 puni 12 temp 1000

Example(4)

----------

Set up and run an adaptive umbrella sampling simulation using an interatomic

distance as a reaction coordinate.