Thermodynamic force fields

Figure 7.6 Plot of the thermodynamic force field, a, versus Wi number for the C50H102 PE melt (T = 450 K, P= 1 atm). (Reproduced with permission from Ref [193].)...

The classical introduction to molecular mechanics calculations. The authors describe common components of force fields, parameterization methods, and molecular mechanics computational methods. Discusses th e application of molecular mechanics to molecules comm on in organic,and biochemistry. Several chapters deal w ith thermodynamic and chemical reaction calculations. 

Lsc th e force fields th at have dern on strated accuracy for particu lar molecules or simulations. For example, CiPLS reproduces physical properties in liquid simulations extremely well. MM+ reproduces the structure and thermodynamic properties of small, nonpolar molecules better than AMBER, BIO+, and OPLS. 

Calculating Thermodynamic Properties Using a Force Field... 

T and N L Allinger 1989. Molecular Mechanics. The MM3 Force Field for Hydrocarbons. 2. Vibra-ional Frequencies and Thermodynamics. Journal of the American Chemical Society 111 8566-8582. on F 1930. Zur Theori und Systematik der Molekularkrafte. Zeitschrift fur Physik 63 245-279. 

This text is similar to that of McCammon and Harvey (see below), but also provides a background for force field-based calculations and a more sophisticated discussion. Includes numerous examples of computing the structure, dynamics, and thermodynamics of proteins. The authors provide an interesting chapter on the complementary nature of molecular mechanics calculations and specific experimental techniques. 

Protein-DNA complexes present demanding challenges to computational biophysics The delicate balance of forces within and between the protein, DNA, and solvent has to be faithfully reproduced by the force field, and the systems are generally very large owing to the use of explicit solvation, which so far seems to be necessary for detailed simulations. Simulations of such systems, however, are feasible on a nanosecond time scale and yield structural, dynamic, and thermodynamic results that agree well with available experimen-... 

Molecular mechanics calculations with the molecular mechanics force field program were performed to compare thermodynamic stability among araguspongine B (17) (containing two cw-fused perhydropyrido[2,l-Z>] [l,3]oxazine bicycles), araguspongine D (18) (containing two tran -fused perhydropyrido[2,l-Z)][l,3]oxazine bicycles), and araguspongine E (19)... 

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]. 

Jorgensen et al. has developed a series of united atom intermolecular potential functions based on multiple Monte Carlo simulations of small molecules [10-23]. Careful optimisation of these functions has been possible by fitting to the thermodynamic properties of the materials studied. Combining these OPLS functions (Optimised Potentials for Liquid Simulation) with the AMBER intramolecular force field provides a powerful united-atom force field [24] which has been used in bulk simulations of liquid crystals [25-27],... 

Grossfield A, Ren PY, Ponder JW (2003) Ion solvation thermodynamics from simulation with a polarizable force field. J Am Chem Soc 125(50) 15671—15682... 

Modified force field models based on path integral simulations yield excellent agreement with experiment for thermodynamic properties. 

As computers become even faster and force fields expand to cover more types of molecules, both MDFE and simplified methods will be increasingly useful. The most fruitful approach will be to use a spectrum of methods, both for ligand design and for fundamental studies of biomolecular thermodynamics. 

Most of the force fields described in the literature and of interest for us involve potential constants derived more or less by trial-and-error techniques. Starting values for the constants were taken from various sources vibrational spectra, structural data of strain-free compounds (for reference parameters), microwave spectra (32) (rotational barriers), thermodynamic measurements (rotational barriers (33), nonbonded interactions (1)). As a consequence of the incomplete adjustment of force field parameters by trial-and-error methods, a multitude of force fields has emerged whose virtues and shortcomings are difficult to assess, and which depend on the demands of the various authors. In view of this, we shall not discuss numerical values of potential constants derived by trial-and-error methods but rather describe in some detail a least-squares procedure for the systematic optimisation of potential constants which has been developed by Lifson and Warshel some time ago (7 7). Other authors (34, 35) have used least-squares techniques for the optimisation of the parameters of nonbonded interactions from crystal data. Overend and Scherer had previously applied procedures of this kind for determining optimal force constants from vibrational spectroscopic data (36). 

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