MMX force field calculations

Vinylindoles have been studied extensively and used in the synthesis of carbazoles, alkaloids and other classes of pharmacologically active compounds. MMX force field calculations have shown that coplanar s-cis and. s-trans conformations of 3-vinylindole (84, Figure 2.11) are the most stable conformers they exhibit only slight differences in their thermodynamic stabilities [86]. 

Indeed, MMX force-field calculations place the product roughly 5.5 kcal/mol higher in enthalpy than the starting diene. ... 

MMX force-field calculations " suggest that the reaction is exothermic by 25 kcal/mol, so there must be a very negative reaction entropy associated with the cyclization which is not unreasonable. 

MMX force-field calculations are also given in italics in Scheme 13.21. ... 

A summary of all the reactions reported in the (CH)i2 series is given in Scheme 13.22 along with the RHF/6-31G calculations and MMX force-field calculations of the heat of formation relative to two benzene molecules. The experimental activation free energies are given over the arrows. 

PC Model has some features that are not found in many other molecular mechanics programs. This is one of the few programs that outputs the energy given by the force field and the heat of formation and a strain energy. Atom types for describing transition structures in the MMX force field are included. There is a metal coordination option for setting up calculations with metal atoms. There are also molecular similarity and conformation search functions. 

The performance is (as expected) very good. MMX provides relative (and absolute) stabilities with a MAD of only 1.2 kcal/mol, which is better than the estimates from the combined theoretical methods in Table 11.31. Considering that force field calculations require a factor of 10 less computer time for these systems than the ab initio methods combined in Table 11.31, this clearly shows that knowledge of the strengths and weakness of different theoretical tools is important in selecting a proper model for answering a given question. 

Note (a) The relative energy difference AG° = (energy of structure A) - (energy of structure B). The energies of structures 6A-12A, and 6B-12B were calculated using the MMX force-field in PCMODEL. 

Semiempirical and molecular mechanics calculations have been widely used. Thus, conformation of indolo benzazepine 423 (Figure 8) with its conjugated benzo and indole rings has been studied by molecular mechanics (MMX force field). Its planarity was estimated from a calculation of dihedral angle Ti 2 3 4 the value of ca. 22° is due to strain as contributed by azepine ring. This characteristic was further compared to that of the open-chain and six-membered... 

For CH3SC50 four local conformational minima are obtained by molecular mechanics calculations using the MMX force field (Figure 6.4) [7]. Thereby, as shown in Figure 6.4, the asymmetric conformation for this radical is preferred. 

The molecular mechanics method is extremely parameter dependent. A force field equation that has been empirically parameterized for calculating peptides must be used for peptides it cannot be applied to nucleic acids without being re-parameterized for that particular class of molecules. Thankfully, most small organic molecules, with molecular weights less than 800, share similar properties. Therefore, a force field that has been parameterized for one class of drug molecules can usually be transferred to another class of drug molecules. In medicinal chemistry and quantum pharmacology, a number of force fields currently enjoy widespread use. The MM2/MM3/MMX force fields are currently widely used for small molecules, while AMBER and CHARMM are used for macromolecules such as peptides and nucleic acids. 

Force field calculations were done with PCMODEL 4.0 (Serena Software, Bloomington, IN, USA) using the MMX-force field... 

The lack of correlation between cyclization stereoselectivity and the steric energy of the products (calculated by the MMX force field)... 

There are a variety of PC-based programs that perform molecular mechanics calculations. They include PCMODEL, " which uses the MMX force field that is very similar to the MM2 force field but includes parameters for transition metals, MOBY,2 which has its own force field but directed toward... 

PCMODEL contains sixty atom types and generalized parameters, as well as functions and parameters for transition metals, and thus the built-in MMX force field minimizations provide some of the most complete molecular modeling available. Unrestricted Hartree-Fock tt calculations for conjugated systems provide unparalleled accuracy for molecular mechanics calculations of open-shell species. Standard RHF n calculations can be used to model closed-shell species containing carbon, nitrogen, and oxygen. Also, specific aromatic carbon types provide excellent aromatic geometries without n calculations. 

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