The RXNCOR module in CHARMM was initially implemented by J. Kottalam in December 1990 for molecular dynamics simulations with an umbrella potential. The code and this documentation are currently being updated by Aaron R. Dinner and co-workers for use in all situations in which sampling based on (single or multiple) (scalar or vector) order parameters are desired. See tps.doc for additional notes.

All the commands invoking this module are prefixed by the keyword RXNCord. The geometrical elements such as points, lines and planes are referenced by names selected by the user.

```
RXNCoor < set-spec | bas-spec | wri-spec | umbr-spec | defi-spec >
set-spec ::= SET [ NRXN 1 ] NRXN{ name }
where NRXN{ name } is an NRXN-long list of the names of
the order parameters to calculate.
bas-spec ::= BASIn NRXN{ name alo ahi blo bhi } (for TPS and/or SMD)
wri-spec ::= < WRITe [ UNIT unit (default is outu) ] |
TRACe name [ UNIT unit (default is outu) ] >
umbr-spec ::= UMBRella FORM form KUMB ku DEL0 del0 PERIod period SMDDel smddel
stat-spec ::= STATistics LOWDelta lowdel HIDElta hidel DELDelta deldel -
START start
defi-spec ::= DEFIne name geom-spec
geom-spec ::= POINt [MASS] atom_selection
DIREction point1 point2
direction1 direction2
LINE THROugh point1 THROugh point2
PARAllel_to line1
PERPend line1 PERP line2
NORMal_to plane1
PLANe THROugh point1 THRO point2 THRO point3
CONTaining line1
PERPendic line1
PARAllel line1 PARA line2
plane1
DISTance point1 point2
line
plane
ANGLe direction1 direction2 direction3
line1 line2 direction3
line1 plane2 direction3
plane1 plane2 direction3
RATIo distance1 distance2
COMBination name1 weight1 name2 weight2 ...
SCOMbination name1 mult1 name2 mult2 ...
VCOMbination name1 mult1 name2 mult2 ...
```

A distance can be between two points or the perpendicular distance of a point from a plane or a line. An angle can be between two (intersecting or non-intersecting) lines and so on. Planes and lines are ultimately defined in terms of points and points can be defined as the centres of geometry (or mass) of a groups of atoms in the macromolecule. Thus we have in CHARMM a general algorithm to define any order parameter (of the above form) in terms of the cartesian coordinates of arbitrary sets of atoms.

The name immediately following the DEFIne keyword is the name of the object being defined. Names referenced towards the right side are names of objects already defined.

If the MASS keyword appears in the POINt definition, then the point is the centre of mass, otherwise it is the centre of geometry.

The order of points in DIREction definition is important, unlike in DISTance definition. When two directions are used to define a third direction, the third direction is perpendicular to the other two.

The ANGLe is the one subtended by the first two arguments measured anti- clockwise when viewed along direction3. The angle defined with a line and plane is the one between the line and the plane normal, NOT the plane itself.

RATIo is distance1/distance2.

COMBination is the weighted mean of all names; SCOMbination is the simple sum mult1*name1+mult2*name2...; VCOMbination is a vector analog of SCOMbination, where three-dimensional vectors can be combined with arbitrary weighting to define another vector.

The SET command sets a particular geometric element as the reaction coordinate. This element must be already defined. If a name is referenced and not defined, the program will stop. If a name is defined but not referenced, no message is issued, but this will result in some unnecessary computations without affecting the results.

The UMBR commad specifies the form and parameters for an umbrella potential:

form | functional form of potential |
---|---|

1 | ku*(delta-del0)**2 |

5 | ku*(delta-del0)**2 + Ubias(delta) |

In form 5, Ubias is a biasing potential, used in addition to the harmonic restraining potential, to truncate high barriers of activated processes. Ideally, Ubias(Rc) would be the negative of the potential of mean force g(Rc), where Rc is the reaction coordinate. Ubias is implemented as a cubic spline function based on a tabulated data to be read prior to the call of RXNC.

Order parameters can be periodic. To ensure correct calculation of the energy and forces, set the PERIod keyword to a non-zero value.

The STAT subcommand specifies the range of a coordinate and when to collect statistics. Starting from the ‘start’-th step of dynamics, the number of occurences of delta (the value of each reaction coordinate) will be counted in each interval ‘deldel’ long. This counting will be done in the range ‘lowdel’ to ‘hidel’. The statistics collected by the STAT subcommand are printed out at the end of dynamics when the WRITe subcommand has been invoked.

WRITe will print out a table without any header. The header is left out on purpose to enable this file to be read by any plotting program. The meanings of the numbers are therefore explained here. Recall that the STAT subcommand essentially setup a range of the reaction coordinate (delta) and divided this range into small pieces. For each piece the following information is printed out in one line:

```
the midpoint of the delta interval
the free energy at this midpoint (after subtracting the umbrella potential)
the number of observations for which delta fell in this interval.
(One observation is made at every step of the dynamics)
```

Apart from the cumulative statistics, it may be useful to have a print out of the delta values versus time. The time series of any quantity defined by the DEFIne subcommand can be printed by using the TRACe subcommand. This command should appear before the dynamics command.

As an example, consider the interconversion between the chair and boat forms of cyclohexane. This process can be described in terms of three rotation angles. These angles rotate carbons 2, 4 and 6 respectively about the plane of carbons 1, 3 and 5.

Let us number the carbon atoms in cyclohexane as C1,...,C6. Consider the plane of atoms c1, c3 and c5 and the plane of atoms c1, c2 and c3. Let us call the angle between these two planes as a rotation angle. There are two other rotation angles about the c1-c3-c5 central plane. The mean of these three rotation angles serves as a reaction coordinate for the chair-boat conversion.

```
rxncor: define c1 point select atom cycl 1 c1 end
rxncor: define c2 point select atom cycl 1 c2 end
rxncor: define c3 point select atom cycl 1 c3 end
rxncor: define c4 point select atom cycl 1 c4 end
rxncor: define c5 point select atom cycl 1 c5 end
rxncor: define c6 point select atom cycl 1 c6 end
rxncor: define d13 direction c1 c3
rxncor: define d35 direction c3 c5
rxncor: define d51 direction c5 c1
rxncor: define d12 direction c1 c2
rxncor: define d34 direction c3 c4
rxncor: define d56 direction c5 c6
rxncor: define norc direction d35 d13
rxncor: define nor1 direction d13 d12
rxncor: define nor2 direction d35 d34
rxncor: define nor3 direction d51 d56
rxncor: define alf1 angle norc nor1 d13
rxncor: define alf2 angle norc nor2 d35
rxncor: define alf3 angle norc nor3 d51
rxncor: define mean combi alf1 1.0 alf2 1.0 alf3 1.0
rxncor: set mean
```

An example of the use of FORM 5 is shown below:

```
...
rxncor: define RC distance PCC PCO
rxncor: set RC
open read unit 33 form name bias.pot
rxncor: bias unit 33
close unit 33
rxncor: umbrella kumb 20. del0 1.50 form 5
...
WHERE bias.pot contains:
* Trial Biasing Potential
* example, 1200
*
5 ! number of points (up to 25)
1.0 -28.0 ! Rc Ubias(Rc)
1.3 -18.0
1.4 -8.0
1.5 0.0
1.6 -2.0
END description of FORM 5 JG 12/00
```

In each case, dynamics is run by invoking the DYNAmics command. See tps.doc for notes on using RXNCOR with transition path sampling and steered molecular dynamics.

To extract results from umbrella sampling simulations, return to the example of cyclohexane

```
rxncor: trace alf1 unit 22
rxncor: trace alf2 unit 23
rxncor: trace alf3 unit 24
rxncor: trace mean unit 25
rxncor: umbrella kumb 15.0 form 1 del0 -0.4
rxncor: statistics lowdelta -0.6 hidelta -0.4 deldel 0.002 start 5000
dynamics rest nstep 15000 firstt 300.0 finalt 300.0 ihtfrq 0 -
teminc 0.0 iunwrite 19 kunit 20 iunread 17
rxncor: write unit 21
close unit 21
```

Here, the essential results are the first and second columns of the output from the WRITe subcommand, which plot free energy versus the order parameter in the covered range of the order parameter values (delta values). In order to cover the full range of delta the procedure is repeated by constraining delta around a particular value by using an umbrella potential centered at that value.

For theory and practice of umbrella sampling, see Kottalam and Case in Journal of American Chemical Society, 110, 7690 (1988)