Molecular force-field parameters

The modeling of inorganic compounds in general is gaining more and more interest [25-28]. The authors of MOMEC addressed this in a monograph describing how molecular modeling techniques can be applied to metal complexes and how the results can be interpreted [29]. The current force field parameter set is available on the author s web site. 

M. Jalaie, K. B. Lipkowitz, Published force field parameters for molecular mechanics, molecular dynamics, and Monte Carlo simulations, in Reviews in Computational Chemistry, Vol. 14, K.B. Lipkowitz, D. B. Boyd (Eds.), Wiley-VCH, New York, 2000, pp. 441-486. 

Halgren T A 1996b. Merck Molecular Force Field II MMEF94 van der Waals and Electrostatic Parameters for Intermolecular Interactions. Journal of Computational Chemistry 17 520-552. 

Most existing molecular mechanics studies of inorganic molecules required careful customization of force field parameters. 

In computational chemistry it can be very useful to have a generic model that you can apply to any situation. Even if less accurate, such a computational tool is very useful for comparing results between molecules and certainly lowers the level of pain in using a model from one that almost always fails. The MM+ force field is meant to apply to general organic chemistry more than the other force fields of HyperChem, which really focus on proteins and nucleic acids. HyperChem includes a default scheme such that when MM+ fails to find a force constant (more generally, force field parameter), HyperChem substitutes a default value. This occurs universally with the periodic table so all conceivable molecules will allow computations. Whether or not the results of such a calculation are realistic can only be determined by close examination of the default parameters and the particular molecular situation. ... 

The parameters in molecular force fields (e.g., Kb, Ke, A, and B) can be determined by using them to calculate different independent molecular... 

Halgren TA. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J Comput Chem... 

The usefulness of quantum-chemical methods varies considerably depending on what sort of force field parameter is to be calculated (for a detailed discussion, see [46]). There are relatively few molecular properties which quantum chemistry can provide in such a way that they can be used directly and profitably in the construction of a force field. Quantum chemistry does very well for molecular bond lengths and bond angles. Even semiempirical methods can do a good job for standard organic molecules. However, in many cases, these are known with sufficient accuracy a C-C single bond is 1.53 A except under exotic circumstances. Similarly, vibrational force constants can often be transferred from similar molecules and need not be recalculated. 

The monoketone bis(2,2, /V,/V -bipyridyl)ketone forms a [CoinL2]+ complex on reaction with [Co(NH3)4(C03)]+ in water.981 As reported for a quite different Co11 complex, the ketone is hydrated to form the gem diol which binds as a monodeprotonated O-donor along with the two pyridine groups in a tridentate chelate, with very little distortion from octahedral observed in the complex. This appears to represent a facile route for this type of inherently poor donor to achieve coordination. Chelated /3-diketonate anions are long-studied examples of O-donor chelates, and continue to be examined. A simple example is the m-[Co(acac)2(NH 3)2]1 (acac = 2,4-pentane-dionate), structurally characterized and utilized to produce molecular mechanics force field parameters for /3-diketones bound to Co111.982... 

The calculations described here have been called strain calculations, molecular mechanics, or force field calculations. We prefer the latter term. For a discussion of historical developments and a literature survey of earlier work, which are not given here, the reader is referred to a number of other reviews (1-3). The present paper deals with the description of force field types, techniques of energy minimisation, and procedures for the determination of force field parameters, and with some applications, preferentially taken from our own field of interest. In accordance with the experiences of the author, the work of Lifson and coworkers is given special attention other authors are nevertheless well represented in the context of critical comparisons. We hope that this selection, although inevitably biased, will help to improve the consistency of the presentation of the subject. 

One example of the use of semiempirical methodology is provided in an article detailing a molecular-dynamics simulation of the beta domain of metallothionein with a semiempirical treatment of the metal core.73 The beta domain of rat liver metallothionein-2 contains three-metal centers. In this study, three molecular variants with different metal contents—(1) three cadmium ions, (2) three zinc ions, and (3) one cadmium ion and two zinc ions—were investigated using a conventional molecular dynamics simulation, as well as a simulation with a semiempirical quantum chemical description (MNDO and MNDO/d) of the metal core embedded in a classical environment. For the purely classical simulations, the standard GROMOS96 force-field parameters were used, and parameters were estimated for cadmium. The results of both kinds of simulations were compared to each other... 

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

The strategy in a molecular dynamics simulation is conceptually fairly simple. The first step is to consider a set of molecules. Then it is necessary to choose initial positions of all atoms, such that they do not physically overlap, and that all bonds between the atoms have a reasonable length. Subsequently, it is necessary to specify the initial velocities of all the atoms. The velocities must preferably be consistent with the temperature in the system. Finally, and most importantly, it is necessary to define the force-field parameters. In effect the force field defines the potential energy of each atom. This value is a complicated sum of many contributions that can be computed when the distances of a given atom to all other atoms in the system are known. In the simulation, the spatial evolution as well as the velocity evolution of all molecules is found by solving the classical Newton equations of mechanics. The basic outcome of the simulation comprises the coordinates and velocities of all atoms as a function of the time. Thus, structural information, such as lipid conformations or membrane thickness, is readily available. Thermodynamic information is more expensive to obtain, but in principle this can be extracted from a long simulation trajectory. 

Mehran Jalaie and Kenny B. Lipkowitz, Appendix Published Force Field Parameters for Molecular Mechanics, Molecular Dynamics, and Monte Carlo Simulations. 

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