Molecular mechanics models limitations

Notice that in these models metal atoms are not currently included, because the theoretical methods used for modeling (particularly molecular mechanics methods) limit the type of atoms and the number of atoms (molecular size) which may be calculated. 

Molecular mechanics models differ both in the number and specific nature of the terms which they incorporate, as well as in the details of their parameterization. Taken together, functional form and parameterization, constitute what is termed a force field. Very simple force fields such as SYBYL, developed by Tripos, Inc., may easily be extended to diverse systems but would not be expected to yield quantitatively accurate results. On the other hand, a more complex force field such as MMFF94 (or more simply MMFF), developed at Merck Pharmaceuticals, while limited in scope to common organic systems and biopolymers, is better able to provide quantitative accounts of molecular geometry and conformation. Both SYBYL and MMFF are incorporated into Spartan. 

This type of selectivity originates solely from steric interactions between the auxiliary ligands, polymer chain, and the incoming propene. It was first explained qualitatively by means of visualization of the structure of the catalyst precursors. A more quantitative approach led naturally to molecular mechanics models in order to explain and even predict the stereospecificity of catalysts with different ligand environments. Due to the limitations of MM models to describe metallocene complexes as well as bond breaking and bond formation processes (see Section 3.1.2.1), the models were initially based on some rigid core structures derived from the measured structures, e. g., of the dichloride precursors [25, 26]. In order to achieve more accurate results, core structures, calculated by ab initio methods, were employed later. A further step in this direction is the joint description of the... 

The molecular mechanics model is extremely popular among chemists and there is an overwhelming number of articles reporting the application of this method. Their broad application also is considered to raise our understanding and our capability to explain the structural features of the treated molecules.5 But still, as the last example shows, there exist upper limits concerning the size of the molecules for which a proper prediction of structure can be made. Especially in the case of proteins, such predictions can have tremendous practical importance. The last model, I discuss is a method used to predict the secondary structure of a protein, i.e., its folding mode, starting with only information on its primary structure, i.e., its amino acid sequence. 

The most severe limitation of ah initio methods is the limited size of the molecule that can be modeled on even the largest computers. Semiempirical calculations can be used for large organic molecules, but are also too computation-intensive for most biomolecular systems. If a molecule is so big that a semiempirical treatment cannot be used elfectively, it is still possible to model its behavior avoiding quantum mechanics totally by using molecular mechanics. 

Molecular mechanics methods have only been used to a limited extent for these classes of compounds. However, molecular mechanics methods do fairly well in describing the geometries and relative energies of compounds with these elements. It is perhaps only for historical and economic reasons that molecular mechanics has not been used more for modeling these elements. Subsequently, there are not as many force fields available. 

This article reviews progress in the field of atomistic simulation of liquid crystal systems. The first part of the article provides an introduction to molecular force fields and the main simulation methods commonly used for liquid crystal systems molecular mechanics, Monte Carlo and molecular dynamics. The usefulness of these three techniques is highlighted and some of the problems associated with the use of these methods for modelling liquid crystals are discussed. The main section of the article reviews some of the recent science that has arisen out of the use of these modelling techniques. The importance of the nematic mean field and its influence on molecular structure is discussed. The preferred ordering of liquid crystal molecules at surfaces is examined, along with the results from simulation studies of bilayers and bulk liquid crystal phases. The article also discusses some of the limitations of current work and points to likely developments over the next few years. 

The lattice gas has been used as a model for a variety of physical and chemical systems. Its application to simple mixtures is routinely treated in textbooks on statistical mechanics, so it is natural to use it as a starting point for the modeling of liquid-liquid interfaces. In the simplest case the system contains two kinds of solvent particles that occupy positions on a lattice, and with an appropriate choice of the interaction parameters it separates into two phases. This simple version is mainly of didactical value [1], since molecular dynamics allows the study of much more realistic models of the interface between two pure liquids [2,3]. However, even with the fastest computers available today, molecular dynamics is limited to comparatively small ensembles, too small to contain more than a few ions, so that the space-charge regions cannot be included. In contrast, Monte Carlo simulations for the lattice gas can be performed with 10 to 10 particles, so that modeling of the space charge poses no problem. In addition, analytical methods such as the quasichemical approximation allow the treatment of infinite ensembles. 

The molecular mechanics method is usually limited to the determination of molecular geometry and thermodynamic quantities. However, it is sometimes employed to estimate vibrational frequencies - at least in those cases in which 7r electrons are not involved in the determination of the molecular geometry. It should be emphasized that this method, as well as those presented in Chapter 12, are applicable only to isolated molecules, as intermolecular forces are not included in the model. 

Molecular mechanics is a useful and reliable computational method for structure, energy, and other molecular properties. The mathematical basis for molecular models in MM3 has been described, along with the limitations of the method. One of the major difficulties associated with molecular mechanics, in general, and MM3 in particular is the lack of accurately parameterized diverse functional groups. This lack of diverse functional groups has severely limited the use of MM3 in pharmaceutical applications. 

Some models carry the surface tension approach to extreme, and attempt to include even the electrostatic contributions in the surface tensions. These pure SASA models are obviously limited in their ability to account for such phenomenon as dielectric screening, but they have the virtue of being very easy to compute. Thus, they can be used to augment molecular mechanics calculations on very large molecules with a qualitative accounting for solvation. 

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