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                       Force Field Evaluation Suite
                       ----------------------------

                        Dr. Thomas A. Halgren
                        Merck and Co., Inc.
                        Building 50SW-100
                        P.O. Box 2000
                        Rahway, NJ 07065

                        Phone:  732-594-7735
                        Fax:    732-594-4224
                        E-Mail: halgren@merck.com

This evaluation suite is geared to assessing the performance of molecular force 
fields for (1) conformational energies and (2) intermolecularinteractions, but
the molecular structure data it includes could also be used to test the 
accuracy of force-field optimized molecular geometries.  The suite provides 
input data and a summary of principal results for the following manuscript:

T. A. Halgren, "MMFF VII. Characterization of MMFF94, MMFF94s, and Other
Widely Available Force Fields for Conformational Energies and for
Intermolecular-Interaction Energies and Geometries," J. Comput. Chem., 
in press (expected out in April 1999).

In addition to MMFF94 and MMFF94s, the paper characterizes the CFF95, CVFF, MSI
CHARMM, CHARMM 22 (in part) AMBER*, OLPS*, MM2*, and MM3* force fields. Force 
fields excluded because they were unavailable at Merck include AMBER 4, OPLS-AA, 
GROMOS, MM2, MM3, and MM4.  This evaluation suite has been posted so that the 
community can use it to characterize these and other force fields.  The data 
may also be useful for developing or validating new force fields.

The manuscript makes three sets of conformational energy comparisons. The first 
uses the 37 comparisons to experiment employed in the original MMFF94 paper on 
this subject [1].  It also compares the ability of theoretical methods 
ranging from HF/6-31G* to GVB-LMP2/cc-pVTZ(-f) to reproduce the same 
experimental data.  The second set consists of 19 comparisons taken from 
Gundertofte et. al [2] for which neither ab initio nor experimental data were 
used in the development of MMFF94.  The third set consists of 147 comparisons 
to ab initio values obtained at the composite "MP4SDQ/TZP" level [1].

The comparisons for intermolecular-interaction energies and geometries employ
scaled HF/6-31G* results for the 66 small-molecule dimers used in the nonbonded 
parameterization of MMFF94 [3].  The scaling protocol is defined in a file 
described below.


                Input Structure Files for Conformational Energies
                -------------------------------------------------

The following files supply input molecular structure data:

                           conf-e_37-147.mol2
                           conf-e_37-147.mmd
                           conf-e_19.mol2
                           conf-e_19.mmd

Two formats are provided: "mol2", from Tripos, and "mmd", the designation used
at Merck for BatchMin "dat" files.  We chose these file formats because they
are in fairly widespread use and because they allow explicit single and
multiple bonds to be designated. Unlike file formats more commonly used at
Merck, these formats are limited in that they cannot specify formal-
charge information. However, this information is provided in another file
described below.  The conf-e_37-147.mol2 and conf-e_37-147.mmd files provide 
input for the first (37 membered) and third (147 membered) conformation sets.  
The geometries are MP2(FULL)/6-31G* optimized.  The conf-e_19.mol2 and 
conf-e_19.mmd files are used for the second (19 membered) conformation set.  
These files supply MMFF94-optimized geometries that should provide suitable 
starting points for geometry optimization with other force fields. 


                  Input Files Containing Conformational Energies
                  ----------------------------------------------

Reference energies are given in the following files:

                           conf-e_37-147.energies
                           conf-e_37.expt
                           conf-e_37.mp4sdq_tzp
                           conf-e_37.gvb-lmp2
                           conf-e_19.expt
                           conf-e_147.mp4sdq_tzp

The conf-e_37-147.energies file covers the first and third comparison sets.  
This file gives the 5-character "conformational indices" used to label the
structure and geometry [4].  It also specifies the total MP2/TZP energies and 
the 6-31G# small-basis-set MP3 plus MP4SDQ corrections; these energies are 
summed to obtain the composite "MP4SDQ/TZP" energies that were used to form 
best-available ab initio conformational energy differences in the original 
MMFF94 parameterization [1].  The relationship between the 6-31G# and 6-31G* 
basis sets is noted in the file.  This file also contains a title-card string 
for each structure that indicates its constitution and conformation.  
 
The conf-e_37.expt, conf-e_37.mp4sdq_tzp, and conf-e_37.gvb-lmp2 files specify 
the experimental, "MP4SDQ/TZP", and GVB-LMP2/cc-pVTZ(-f) conformational 
energies for comparison set 1. The experimental conformational energies differ 
in some cases from those used in the earlier work on the derivation of MMFF94 
[1].  An appendix to the paper, which because of space limitations has had to 
be moved to the Supplementary Material (available on line from the J. Comput. 
Chem. server), describes the basis for the choice of these particular 
experimental values and lists some of the others that are available.  The force 
fields examined in the manuscript are compared to each set of reference 
energies.  A summary table described later shows that a given force field fits 
each reference set about equally well (or poorly).  This finding indicates that 
all three sets provide a valid basis for assessing the accuracy of molecular 
force fields.

Finally, the conf-e_19.expt and conf-e_147.mp4sdq_tzp files respectively 
specify the reference experimental and "MP4SDQ/TZP" conformational energies for
comparison sets 2 and 3. The experimental values for comparison set 2 were 
taken from Gundertofte et al. [2] without further examination.



                Other Data Files for Conformational Energies
                --------------------------------------------

                           conf-e_37-147.fc
                           conf_e_19.titles

As previously indicated, formal atomic charge information is not preserved in 
the "mol2" input files and is represented only implicitly in the "mmd" file 
through the assigned MacroModel atom types.  To assist those who may wish to 
utilize file formats that require explicit formal charge specifications, this 
information is provided for comparison sets 1 and 3 in the conf-e_37-147.fc 
file.  Conformation set 2, in contrast, has no instances of non-zero formal 
atomic charges.  The conf_e_19.titles file lists "title card" descriptions of 
the structures and geometries for comparison set 2.


                 Input Files for Intermolecular Interactions
                 -------------------------------------------

                           hbond_monomers.mol2
                           hbond_monomers.mmd
                           hbond_dimers.mol2
                           hbond_dimers.mmd
                           hbond.interactions
                           hbond.energies

The "mol2" and "mmd" input structure files provide HF/6-31G*-optimized monomer 
and dimer geometries.  The hbond.interactions file identifies the monomers that 
form each dimer and specifies the dimer atoms that contribute to key 
hydrogen-bond interactions.  These specifications allow X...Z heteroatom 
distances and X-H...Z hydrogen-bond angles to be computed from the input 
structure files and from optimized force-field structure files derived from
them.  The file also explains the procedure used to obtain the scaled QM 
interaction energies and nonbonded heteroatom distances from the raw HF/6-31G* 
data.  The hbond.energies file lists the raw HF/6-31G* energies for the 
monomers and dimers.

               Other Data Files for Intermolecular Interactions
               ------------------------------------------------

                           hbond_monomers.titles
                           hbond_dimers.titles
                           hbond_monomers.fc
                           hbond_dimers.fc

The "titles" files help to clarify the connection between the 5-character 
conformational indices and the associated structures.  As before, the 
hbond_monomers.fc and hbond_dimers.fc files specify the atoms that carry 
non-zero formal ionic charges.  

                           Summary Tables
                           --------------

                           conf-e_tables.ps
                           hbond_table.ps

These postscript files contain tables taken from the paper.  Each summarizes 
the overall success of the fits to experimental or ab initio data for a range 
of theoretical methods.  

In the conf-e_tables.ps file, the first table documents the differing abilities 
of ab initio methods ranging from HF/6-31G* to GVB-LMP2/cc-pVTZ(-f) to 
reproduce the experimental conformational energies of set 1.  The second table 
shows the ability of the force field models to fit experimental, "MP4SDQ/TZP", 
and GVB-LMP2/cc-pVTZ(-f) conformational energies.  The third table summarizes 
the fit of the force-field conformational energies to the experimental 
conformational energies of set 2, and the fourth summarizes the fit of the 
force-field models to the 147 "MP4SDQ/TZP" conformational energies of set 3.  
The manuscript itself also contains detailed tables that show the result given 
by each theoretical method for each conformational comparison; because of space 
limitations, the detailed results that the fourth table summarizes have been 
relegated to the on-line Supplementary Material.

The table contained in the hbond_table.ps file summarizes the ability of the 
various force fields to reproduce scaled QM interaction energies, scaled QM 
X...Z heteroatom distances, and unscaled QM X-H..Z hydrogen-bond angles.

                                A Request
                                ----------

I have posted this information in the hope that it will help others to test,
or develop, additional force fields.  In return, I ask those who do so to let 
me know of results obtained from its use, to the extent this is feasible.

                                References
                                ----------

1.  T. A. Halgren and R. B. Nachbar, J. Comput. Chem., 17, 587-615
    (1996).
2.  K. Gundertofte, T. Liljefors, P.-O. Norrby, and I. Petterssen, J. Comput.
    Chem, 17, 429-449 (1996).
3.  T. A. Halgren, J. Comput. Chem., 17, 520-552 (1996).
4.  T. A. Halgren, J. Comput. Chem., 17, 490-519 (1996). 

                               File Sizes
                               ----------

 File name                   Size in Bytes
------------------------------------------
 conf-e_147.mp4sdq_tzp               4,508
 conf-e_19.expt                        791
 conf-e_19.mmd                     114,540
 conf-e_19.mol2                     80,207
 conf-e_37-147.energies             27,376
 conf-e_37-147.fc                      628
 conf-e_37-147.mmd                 667,205
 conf-e_37-147.mol2                483,177
 conf-e_37.expt                      1,198
 conf-e_37.gvb-lmp2                  1,218
 conf-e_37.mp4sdq_tzp                1,248
 conf-e_tables.ps                   22,094
 conf_e_19.titles                    1,827
 hbond.energies                      2,526
 hbond.interactions                  3,825
 hbond_dimers.fc                       444
 hbond_dimers.mmd                  111,820
 hbond_dimers.mol2                  81,111
 hbond_dimers.titles                 3,222
 hbond_monomers.fc                     401
 hbond_monomers.mmd                 53,983
 hbond_monomers.mol2                41,007
 hbond_monomers.titles               2,200
 hbond_table.ps                      9,972


Modified: Thu Feb 18 18:49:00 1999 GMT
Page accessed 14225 times since Sat Apr 17 21:16:46 1999 GMT