By default, very close non-bonded atomic pairs will be separated before the energy calculation is done. To override this, specify DEBG flag 33.

arg1 Extent of listing

-1      List the total molecular mechanics energy to the log file only.

0      List the total molecular mechanics energy to the log file and the minimal Energy Summary to the file filename.mmo.

1      List the total molecular mechanics energy to the log file and the complete Energy Listing with all internal coordinate components to the file filename.mmo.

2      List Double and Single Precision molecular mechanics energy to log file only. Used primarily for testing or for short summary of total stretch, bend...etc. energies.

3      Acts like option 0, except, in addition, numerical and analytical surface areas for all atoms are listed to the .mmo file. Surface energies are also given, and are computed using the method specified in arg3.

4      Prints the double precision energy components to the .log file. In the past, this has been possible only in combination with single-precision energies (arg1=2).

0      kJ/mol (default)

1      kcal/mol

0      Use numerical evaluations of atomic surface areas and analytical approximation for Born radii (default).

1      Use fast analytical approximations of surface areas and Born radii.

2      Use numerical evaluations of both surface areas and Born radii.

0      (Default.) Program uses internal criteria to decide whether to update the interaction array.

1      Update the full interaction list.

2      Update nonbondeds only.

arg1 Derivative selection

1      Numerical and analytical first derivatives (default).

2      Numerical and analytical second derivatives.

3      Numerical and analytical first and second derivatives.

4      Analytical (only) first derivatives.

5      Analytical (only) first and second derivatives.

0      Start at atom 1 and give derivatives for entire system.

>0      Start at atom arg2 and give derivatives for rest of system.

<0      Start at atom 1 and give derivatives for atoms through -arg2.

0      All (default)

1      Stretch

2      Bend

3      Torsion (proper and improper)

4      Nonbonded

8      Solvation 1

9      Solvation 2

10      Solvation 3

11      Stretch-bend

12      Bend-bend

13      Stretch-torsion

14      Charge-multipole electrostatics

15      Wilson-angle out-of-plane terms

arg5 Step length (Angstroms) for numerical derivative calculation

ASET - Atom Sets

ASET commands may be issued before a READ, and are in force for all subsequent structures read until or unless cleared or altered. Thus, such commands may be issued before BGIN/END loop, and will be in force for all structures read within the loop.

arg1-4 Atom number

arg5 Set number

arg6 Command mode

0      Add the listed atoms to the set

1      Synonym for 0.

-1      Delete the listed atoms from the set given, if they are in the set. Attempts made to delete atoms from set 0 are ignored.

2      Add the range of atoms between arg1 and arg2 (inclusive) to the set; arg3 and arg4 are ignored.

-2      Delete each atom in the given range from the set, provided it is in the set.

3      Add the molecules containing the atoms given by args1 through 4 to the given set.

-3      Delete the molecule molecule containing the atoms in args1 through 4 from from the set, if they were in it.

ASNT commands may be issued before a READ, and are in force for all subsequent structures read until or unless cleared or altered. Thus, such commands may be issued before a BGIN/END loop, and will be in force for all structures read within the loop.

arg1 Set number or control

>0      The first set number.

<0      The actions encoded in arg3 and arg4 will be applied to all pairs of sets.

>0      The second set number.

<0      The actions encoded in arg3 and arg4 will be applied pairwise to all set combinations including the set encoded in arg1, which must be positive.

0      Turn off force-field interactions between sets.

1      Leave force-field interactions on.

0      Turn off constraint interactions between sets.

1      Leave constraint interactions on.

· ASNT 1 2 0 0     : turns off all interactions between sets 1 and 2.

· ASNT 1 2 0 1     : turns off force-field interactions but retains constraint interactions between sets 1 and 2.

· ASNT 2 -1 0 0     : turns off all interactions between set 2 and other sets.

· ASNT -1 0 1 1     : turns on all interactions between all sets (i.e., restores initial state of the program)

Coulombic components are removed from these interactions, unless DEBG 58 is specified.

VDWB may be used along with the MCMM, LIGB and MOLS commands to perform a configurational search of the coordination sphere. TORS and, if applicable, RCA4 commands can be added to explore theinternal conformational space of the ligands at the same time.

arg1 Central atom

arg2 Outer atom

0      All bends with arg1 as the central atom with be replaced with vdW interactions.

>0      Arg3 must also be greater than 0. In this situation, the arg2-arg1-arg3 bond will be replaced by a vdW interaction.

<0      Arg3 must also be less than 0. In this situation, if arg1 already has some bends on the VDWB list, the ABS(arg2)-arg1-ABS(arg3) bend is removed. If no such list exists for arg1, one is created, and all bends centered on arg1 are placed on it except ABS(arg2)-arg1-ABS(arg3).

arg5,6 ro and for the van-der-Waals pairs modeled by VDWB.

Energy Minimization

MINI - MINImize the energy of a structure.

If solvation is used in a minimization, the structure is minimized with analytical approximations to surface areas, but the final energies reported use accurate numerical areas.

If energies change substantially on reminimization or nonbonded updates, use the EXNB command to increase the nonbonded cutoff distances for electrostatics and van der Waals. Alternatively, update more frequently using arg7.

arg1 Minimization mode

<0      Allow uphill motion, using method |arg1|; but implemented only for arg1=4 using no line search (arg2= 0). This facilitates saddle-point searches.

N. B. Starting with MacroModel 6.5, a highly capable explicit saddle-point search method is available, using the SDLP command.

0      Steepest Descent with or without linesearching (SD). Not generally useful except for highly strained structures. Should be used with linesearching (arg2 =1).

1      PR Conjugate Gradient (PRCG) - Best general method. E.Polak and G. Ribiere, Revue Francaise Inf. Rech.Oper., 16-R1, 35 (1969).

3      OS Variable Metric (OSVM). One of the best variable metric methods.
There is no built-in limit on the number of atoms in the molecule when using OSVM. S.S. Oren and E. Spedicato, Math. Programming, 10, 70 (1976).

4      Full Matrix NR (FMNR) - Best method for fully converging molecules.
There is no built-in limit on the number of atoms in the molecule when using FMNR. Gradient must be small before using this method. Use with linesearching if gradient >0.5 kJ/A-mol.

9      Truncated Newton (TNCG) - Superb method for flexible structures.
There is no built-in limit on the number of atoms in the molecule when using TNCG. J.W. Ponder and F.M. Richards, J. Comput. Chem., 8, 1016 (1987). See arg6.

10      Limited Broyden-Fletcher-Goldfarb-Shanno(LBFGS) - LBFGS can be specified by MINI arg1=10. Experiments so far have not shown superiority of this method above all others; however, we expect to improve the implementation as time goes on, as we feel this method has great potential.

0      Default linesearching

1      For SD or FMNR or LBFGS, turns on line searching. Although LBFGS can be used with line search, it is not recommended in the current implementation.

For PRCG, selects 3-point line searcher (use with problematic structures)

For TNCG, selects original line searcher (try for problematic structures)

arg4 "Energy code" (see DEMX)

Arg5 behaves somewhat differently if FMNR is specified without line-searching (arg1=4, arg2=0). Then, by default (arg5=0.0), the algorithm takes its full step-size, which is the estimated distance to the minimum determined by a harmonic fit to the potential-energy surface. This corresponds to the ordinary meaning of arg5 for other methods. This distance will be too great (for example, it may overshoot the minimum) unless one is already close to a minimum. If a non-zero value is placed into arg5 when this minimization method is specified, the arg5 value will be used as the maximum distance in Angstroms that any atom can move in a single step. If the normal FMNR algorithm calls for a larger step, then all coordinate motions will be scaled back by the ratio of the arg5 value to the maximum atomic displacement called for by the normal algorithm. Experimentation is usually called for to determine a good non-default value for arg5, but if the gradient at the start of FMNR has already been reduced to less than about 10 kJ/mol.Å, a value in the range 0.1 to 1 Å is a good starting point. Provided the gradient is already reasonably low (for example, by virtue of an earlier conjugate-gradient minimization with "loose" convergence), this option permits convergence to a saddle point, since FMNR actually tends toward singularities of any sort, not just minima.

arg6 TNCG Hessian cutoff.

Default is 0.5 kJ/mol-Å2. (This is a new default in MacroModel 6.5.) Smaller values (e.g. 0.1, 0.01) slow iterations but improve the convergence properties of the method.

arg7 Maximum movement (Å) before nonbonded update.

arg8 Reporting interval.

0      (Default.) No intermediate reporting, unless DEBG 1 has been specified.

n      n>0 If n is an integer, report the energy, RMS gradient, and the RMS atomic movement every n steps. If n is not an integer, then the maximum atomic movement and the maximum absolute gradient component are reported, in addition to the reporting of energy, RMS gradient, and the RMS atomic movement. Overrides reporting interval set by DEBG 1.

arg1 Type of criterion

0      Iterate until max number of iterations has been achieved.

1      Energy convergence..

2      Derivative convergence (default if no CONV record appears).

3      Movement convergence.

0      1.0

1      0.1

n      10^-n

SUBS - Define a SUBStructure for subsequent minimization.

· To "tether" part of a molecule in space; this is ordinarily done using FXAT commands but no SUBS commands.

· To save computing time by ignoring part of the system believed to be irrelevant. If both SUBS and FXAT commands appear, then atoms specified in neither command are completely ignored in the simulation.

· When SUBS and FXAT commands appear together, any interaction except a stretch consisting only of FXAT atoms will be eliminated, provided the following conditions hold: 1. the FXAT atoms in question are not specified by any SUBS command; 2. the flat-bottom half-width is zero for all the FXAT atoms concerned; 3. DEBG flag 17 is not specified. The elimination of these interactions saves time, since FXAT atoms will not move much; however, stretches are always included, since, without them, the "fixed" atoms tend to adopt unrealistic relative positions even for rather high tethering potentials.

Prior to Version 6.0, an additional required condition for the elimination of such interactions was that there be at least one atom in the system not specified by either a FXAT or a SUBS command. If a SUBS command appears in the .com file with a zero-valued first argument, then BatchMin will look for a file having the name filename.sbc, in which it will expect to find SUBS and FXAT commands. This file can be produced either manually or using the MacroModel graphical substructure editor. Additional SUBS commands with atom numbers can be used to direct additional atoms to be added to the set in the .sbc file. A typical use of both SUBS formats simultaneously might be simulating the binding of a large molecule to a list of small molecules. The .sbc file might define the substructure and fixed atoms for the large molecules. The first SUBS command in the .com file would have a zero-valued first argument and would set up the substructure for the large molecule. Subsequent SUBS commands would then be used to fully include the small molecule(s) in the simulation. The input data file for one job in this series would contain the large molecule first, ensuring that its numbering scheme, like that in the .sbc file, would remain constant over the series of runs.

If a negative number is given for arg1-4, then the entire molecule containing that atom number will be defined as a part of the substructure.

SUBS commands with non-zero first arguments must come after READ commands. SUBS commands with zero first args must come before READ, because the .sbc file is read during structure file reads.

0      obtain information from .sbc file; arg2-4 are ignored.

>0      atom number

>0      atom number

MTST can only be used after a MINI or ELST command, and MTST cannot be used during a MULT run.

The command can be used only on fully minimized structures having MAXFVE or fewer atoms (see Program Capacity in Chapter 2).

arg1 Listing of vibrational frequencies.

0      No listing.

1      Listing to .mmo file.

VIBR - visualize VIBRational modes

This command is allowed only if a MINI has been performed, unless DEBG 211 has been set.

arg1 First mode animated.

0      1 (default).

n      For n>0, use this value instead of default.

0      5 (default).

n      For n>0, use this value instead of default.

0      10 (default).

N      For N>0, use this value instead of default.

0      1.0 (default).

x      For x>0, use this value instead of default.

RRHO can only be used after a MINI or ELST command. RRHO cannot be used with the MULT option or during a Monte Carlo conformational search.

The command can be used only on fully minimized structures having MAXFVE or fewer atoms if vibration is being considered. For a discussion of MAXFVE, see Program Capacity in Chapter 2.

arg1 Print mode

0      Summary of S, Cv and G to log file (default)

1      Detailed listing of thermodynamic parameters to .mmo file and summary of S, Cv and G to log file.

0      Translation, rotation and vibration (default)

1      Rotation and vibration only

2      Translation and rotation only

3      Translation and vibration only

4      Translation only

5      Rotation only

6      Vibration only

arg7 Lower limit for frequency reporting.

SDLP - Saddle point search

It can be shown that in a local coordinate system defined by the eigenvectors of the current Hessian during FMNR optimization, FMNR maximizes the energy along the eigenvectors with negative eigenvalues and minimizes the energy along the eigenvectors with positive eigenvalues. Mode-following is initiated by a short move along a selected low mode of the Hessian of a minimum-energy conformation. At the new point (slightly higher than the minimum energy point) the Hessian is re-evaluated and its eigenvectors are calculated. The eigenvector which is most similar to the starting low-mode eigenvector, i.e., which has the largest overlap with it, is selected as the degree of freedom to be maximized.

Maximization is accomplished by taking a short FMNR step in the local coordinate system defined by the eigenvectors of the new Hessian, but following the selected eigenvector in the reverse (uphill) direction. This procedure is continued, iteratively, always following the ravine eigenvector uphill while following the remaining eigenvaluesin their normal directions, until convergence to a saddle point is achieved. SDLP can be instructed to follow multiple modes, and each mode is followed in both directions. DEBG 94 saves all the intermediate structures in the .out file and colors each mode-following sequence differently for better visualization.

This command is allowed only if a MINI has been performed, unless DEBG 211 has been set.

arg1: First mode to follow

0      Default: 1 (i.e., the eigenvector of lowest frequency)

n>0      Start with the n-th eigenvector.

0      Default: 1 (i.e., only follow a single mode)

n>0      Follow n modes.

0      Default: 100 kJ/mol.

>0      Maximum energy increase [kJ/mol] above the starting energy minimum allowed during saddle point search. The search is aborted if this limit is exceeded.

0      Default: 0.1 Å

>0      Maximum allowed motion in Å.

arg1-4 Atom numbers

arg5 Starting angle

arg6 Final angle

arg7 Angle increment

N= ABS( arg5-arg6)/arg7 +1 The maximum allowable value of N is 100. In the usual use of the DRIV command (i.e. two DRIV commands in a file), N² energy minimizations will be done.

This command is generally used with the SUBS command to fix or freeze the positions of certain atoms at the periphery of the substructure being minimized. See the description of the SUBS command for a description.

When doing substructure (SUBS) calculations with FXAT restraints having no free flatbottom region (arg4 = 0), interactions wholly involving the fixed atoms, other than stretches, are eliminated from the interaction array unless debug switch 17 is set. This is primarily to improve the speed of the computation; when the force constant is large, as it is by default, the FXAT constraints, together with the stretch interactions, maintain reasonable local geometries.

However, when using low force constants to "gently" constrain atomic positions, local geometries will become unreasonable unless debug switch 17 is set. Also, unless mutual interactions between FXAT atoms are active, solvation energies for systems involving FXAT have no absolute meaning, although comparisons between conformers are still meaningful.

When using FXAT commands in molecular dynamics (e.g. doing substructure molecular dynamics), it is appropriate to use substantially reduced force constants (arg5, e.g. 50-100) so that realistic flexibility and rapid thermal equilibration is possible.

If two FXAT commands specify the same atom, the second replaces the first.

A FXAT command must come after READ commands.

arg1 Fixed atom number

0      Clear or modify fixed and/or frozen atom constraints, depending on the values of the other arguments. A typical use for this facility is in homology modeling, when one might want to perform a minimization with frozen or "tight" fixed contraints, then repetitively diminish the constraints and reminimize. When arg1 is 0, the other args are interpreted as follows.

If arg2 is zero, then all fixed and frozen atoms become unconstrained. (This was the only form of modification available prior to MacroModel 6.5, other than atom-by-atom individual replacement of constraints.) If arg2 is positive, then all fixed atoms are affected according to the values of arg4 and arg5; if arg2 is negative, then all frozen atoms are so affected. For arg2 non-zero, then, if arg4 and arg5 are zero, all fixed or frozen atoms are simply unconstrained; if either arg4 or arg5 is non-zero, then the behavior is as follows.

If arg2 is positive, then fixed-atom constraints are modified. If arg5 is negative, all fixed atoms are frozen. Otherwise, if arg5 is positive, all fixed atoms have their force constants multiplied by arg5; e.g., arg5=0.1 lowers the fixed-atom force constants to 1/10 their current values. If arg4 is 0, the current flat-bottom half-widths are unmodified; if arg4 is negative, any flat bottoms are removed; if arg4 is positive, then the current flat-bottom half-widths are multiplied by arg4/10; e.g., arg4=1 lowers the flat-bottom half-widths to 1/10 their current values.

If arg2 is negative, then frozen-atom constraints are modified. If arg5 is positive, all frozen atoms become fixed, instead, with a force-constant of arg5. If arg4 is positive, they receive a flat-bottom half-width of arg4/10.

>0      Specify fixed or frozen status for the atom specified; this may override a previous specification for the same atom. The following arguments are described for normal use; i.e., the meaning is given for arg1 > 0.

arg5 Force constant [kcal / mol Angstrom2]

The units of the force constant are configurable by means of the FIX multiplier in the force-field file in use. Internally, the program uses kJ/mol as its energy unit, so that, after multiplication by the multiplier, FXAT force constants will have these units. Since all force-field files we supply specify a FIX multiplier of 4.184, the units given in the .com file correspond to kcal/mol.

0      500.0 (default).

>0      Use this value instead of default.

<0      "Freeze" this atom - make it completely unmovable. All interactions (including streeches) composed of such atoms will be removed, unless DEBG 17 is specified. Movable atoms will still feel the effect of such atoms.

FXDI - FiX DIstance

Note - With hydrogens bound to carbon in force fields MM2 and MM3, the restraint is applied between the van der Waals positions of the hydrogen (e.g. with a (C)H in MM2, the hydrogen is treated as if it were at a position shifted 8.5% of the C-H bond length toward the C).

If two FXDI commands specify the same atoms, the second replaces the first.

arg1 Atom 1

0      Clear all existing FXDI constraints

1      The corresponding nonbonded interaction is eliminated from the interaction array. Used to allow fixed distances for atoms which are close in space.

If two FXBA commands specify the same bond angle, the second replaces the first.

arg1 Atom 1

0      Clear all existing FXBA constraints

0      Use initial value.

If two FXTA commands specify the same torsion angle, the second replaces the first, unless arg8 is non-zero.

arg1 Atom 1

0      Clear all existing FXTA constraints

>360      The initial value will be used .

0      A standard 1-fold cosine well will be used.

>1      Allows specification of several allowed ranges for the same set of torsion angles, using a method described by Sefler, A. M., Lauri, G. and Bartlett, P. A., "A convenient Method for Determining Cyclic Peptide Conformation from 1D 1H-NMR Information", Int. J. Pept. Prot. Res. (in press). If arg8 is two, for example, ranges around two dihedral angles can be specified in order to enforce constraints obtained from analysis of NMR coupling constants by means of the Karplus equation. In this example, two FXTA commands are expected for the same values of arg1-4. For each such FXTA command, the user should specify a desired central position in arg6 and a flat-bottom half-widths in arg7. When the last specification is read for a given atom set (for example, when the second FXTA interaction is read for an atom set with an arg8 value of two), BatchMin will reset the central angles and half-widths for the set to values that will achieve the user's original input specification. DEBG 14 makes all this visible to the user.

arg1 Mode selection

0      FXTA for all torsions

1      FXTA for all but double bonds

2      FXTA for all but bonds between sp2 atoms.