Tripos 5.2 force field

Alchemy 2000 (we tested Version 2.05) is a graphic interface for running molecular mechanics and semiempirical calculations. Calculations can be done with the built-in Tripos force field or by calling the MM3 or MOPAC programs, which are included with the package. Alchemy is designed by Tripos and sold by SciVision. 

The program is able to do systematic or random conformation searches using the Tripos force field. Conformation searches can include up to eight single bonds and two rings. 

In this molecule only the bond between the steroid skeleton and the aziridine moiety can rotate freely. A molecular mechanics conformational analysis resulted in two low energy conformations (Fig. 9.4, see p. 264), both of which had almost identical potential energy, as calculated in the Tripos force field [10]. 

As in the case of Tripos 5.252, several amino and nitro compounds were retrieved from the CSD and analyzed for their (all) atom movements upon energy minimization. Although the set of 19 amino and nitro compounds calculated with DREIDING is identical to that examined by Tripos 5.2, a direct comparison between the performance of the two force fields is not possible since the former reported RMS movements of all atoms while the latter, of heavy atoms only. The all atom average RMS movement reported by DREIDING for the set of 19 compounds is 0.298 A and the conclusions we derived for the Tripos force field apply also here. Additional results obtained with the DREIDING force field are discussed in Section II.D. 

Typical force fields such as the Tripos force field available in Sybyl or CVFF 24 available in Biosym contain torsional terms tliat have the form ... 

The 3-D artemisinin analogue database was created with Sybyl 6.2 (Tripos Assoc., St. Louis, MO)154 using the reported crystal structure for artemisinin as a template. The structures were minimized using the Tripos force field in Sybyl 6.2, producing structures close to that of artemisinin. To best describe the aromatic side chains of some analogues, as well as the aliphatic nature of the artemisinin backbone, Gasteiger-Htickel charges were calculated for each of the compounds. 

To take into consideration the effect the metalloporphyrin molecule plays in the active conformation of the ligand, the ligand structural conformation was minimized with respect to hemin using the Tripos Force Field. In the minimization process, a certain small amount of translation occurs, the ligand arriving at a... 

Examples are the Tripos force field (22), the COSMIC force field (23), and that of White and Bovill (24), which uses only two atom types, those at the end of the bond to parameterize the torsional potential rather than the four types of the atoms used to define the torsional angle. One has only to consider the number of combinations of 20 atom subtypes taken four at time (160,000) versus two at a time (400) to understand the explosion of parameters that occurs with increased atom sub-types. The simplifying assumption in parameterization of the torsional potential reduces to some extent the quality of the results (25), but allows the use of the simplified force fields (22) in many situations where other force fields would lack appropriate parameters. The situation can become complicated, however. For example, the amide bond is normally represented by one set of parameters, whether the configuration is cis or trans. Experiments data are quite compelling that the electronic state is different between the two configurations, and different parameter sets should be used for accurate results (Fig. 3.1). Only AM-BER/OPLS currently distinguishes between these two conformational states (26). Certainly, the limited parameterization of simplified force fields would not allow accurate prediction of spectra that is more reflective of the dynamic behavior of the molecule. 

CONFORT performs an exhaustive conformational analysis of a molecule [71]. Two different search modes either generate a user-defined number of conformations, or output a maximally diverse set of conformations, which was used in this study. The diversity metric is based on interconformational distances that circumvent the generation of duplicate structures. The conformations are relaxed and optimized by applying only internal coordinates and analytic gradients and by the Tripos force field package. 

The TRIPOS force fields in the SYBYL and Alchemy programs and the Chem-X, CHARMm, and COSMIC force fields all employ a simple harmonic potential (Eq. [1]) for bond stretching/compression. The CVFF, DREIDING, and UFF force fields support a Morse potential as well as a harmonic potential. The harmonic function is the default in DREIDING and UFF. 

CVFF, CHARMm, DREIDING, UFF, and the TRIPOS force fields all use the Lennard-Jones 12-6 functional form for calculations of nonbonded van der Waals interactions (Eq. [12]), whereas CFF uses a Lennard-Jones 9-6 function and MMFF uses a recently developed buffered 14-7 functional form. i... 

Momany and Rone compared the CHARMm, TRIPOS, DREIDING, and MM2 force fields using a subset of conformational energy data (15) from the data set in Ref. 14. The MM2 and TRIPOS 5.2 results were also taken from this earlier study. In addition, 15 experimental rotational barriers were used to test the CHARMm, DREIDING, and TRIPOS force fields, and the CHARMm and DREIDING force fields were tested by means of an additional set of seven rotational barriers. In the subset of 15 items of conformational energy data, nine were for various cyclohexanes. In that study, the DREIDING and TRIPOS... 

Figure 8 clearly shows that MMFF93, MM2, MM3, and the force fields based on them [ MM2 (Chem3D Plus), MMX (PCMODEL), MM2 , and MM3 ] have the best overall results. The harmonic and diagonal force fields including the TRIPOS force fields in Alchemy and SYBYL and the DREIDING... 

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