Molecular mechanics time complexity

Other methods for racemate separation include fractional crystallization of diaster-eomers with optically pure counter ions [304], conglomerate crystallization [305], and various chromatographic techniques incorporating both mobile and stationary chiral phases [306]. All of these techniques involve intermolecular interactions of some kind. While it is theoretically possible to model these, by using molecular mechanics, the complexity of the problems involved have so far been prohibitive when the time required for a thorough design is compared with experimental trial-and-error studies. 

Once the model of a ligand-receptor complex is built, its stability should be evaluated. Simple molecular mechanics optimization of the putative ligand-receptor complex leads only to the identification of the closest local minimum. However, molecular mechanics optimization of molecules lacks two crucial properties of real molecular systems temperature and, consequently, motion. Molecular dynamics studies the time-dependent evolution of coordinates of complex multimolecular systems as a function of inter- and intramolecular interactions (see Chapter 3). Because simulations are usually performed at nonnal temperature (—300 K), relatively low energy barriers, on the order of kT (0.6 kcal), can... 

Taken together, the regulation of time course and extent of receptor desensitization and tolerance development involves complex cellular processes. Detailed understanding of the molecular mechanisms of receptor... 

The second problem also reflects the exceptional difficulty of exploring complex conformational energy surfaces. Quite simply, only the lowest-cost methods are applicable to anything but molecules with only a few degrees of conformational freedom. In practice and at the present time, this translates to molecular mechanics models. (Semi-empirical quantum chemical models might also represent practical alternatives, except for the fact that they perform poorly in this role.) Whereas molecular mechanics models such as MMFF seem to perform quite well, the fact of the matter is, outside the range of their explicit parameterization, their performance is uncertain at best. 

P. W. Brumer As we know, in quantum mechanics, time evolution and coherence are synonymous. Thus, if I see time evolution, then coherences underlie the observation. Hence, in moving my arm I have created a molecular coherence. We should all be asking why this is so easy to create compared to the complex experiments described in these talks Is it due to the closely lying energy levels in large systems If so, then it suggests that experiments on larger molecules would be easier. 

Before any computational study on molecular properties can be carried out, a molecular model needs to be established. It can be based on an appropriate crystal structure or derived using any other technique that can produce a valid model for a given compound, whether or not it has been prepared. Molecular mechanics is one such technique and, primarily for reasons of computational simplicity and efficiency, it is the most widely used. Quantum mechanical modeling of metal complexes with ab-initio or semi-empirical methods often remains prohibitive because these methods are so computationally intensive. The approximations that are introduced in order to reduce central processing unit (CPU) time and allow quantum mechanical calculations to be used routinely are often severe and such calculations are then less reliable. 

Computational approaches to potential energy may be divided into two broad categories quantum mechanics (Hehre et al, 1986) and molecular mechanics (Berkert and Allinger, 1982). The basis for this division depends on the incorporation of the Schrodinger equation or its matrix equivalent. It is now widely recognized that both methods reinforce one another in an attempt to understand chemical and biological behavior at the molecular level. From a purely practical standpoint, the complexity of the problem, time constraints, computer size, and other limiting factors typically determine which method is feasible. 

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