Computational methods limitations

It was reahzed quite some decades ago that the amount of information accumulated by chemists can, in the long run, be made accessible to the scientific community only in electronic form in other words, it has to be stored in databases. This new field, which deals with the storage, the manipulation, and the processing of chemical information, was emerging without a proper name. In most cases, the scientists active in the field said they were working in "Chemical Information . However, as this term did not make a distinction between librarianship and the development of computer methods, some scientists said they were working in "Computer Chemistry to stress the importance they attributed to the use of the computer for processing chemical information. However, the latter term could easily be confused with Computational Chemistry, which is perceived by others to be more limited to theoretical quantum mechanical calculations. 

Simply doing electronic structure computations at the M, K, X, and T points in the Brillouin zone is not necessarily sufficient to yield a band gap. This is because the minimum and maximum energies reached by any given energy band sometimes fall between these points. Such limited calculations are sometimes done when the computational method is very CPU-intensive. For example, this type of spot check might be done at a high level of theory to determine whether complete calculations are necessary at that level. 

The search for the optimum can involve many case studies. Often, if time is limited, a rigorous canned computer program is utilized. However, this is expensive. If time is not as much of a factor, the method prevented here will allow the calculations to be handled conveniently by hand or computer having limited core. 

The Smith-Brinkley Method can therefore be used to generate a hand base case beginning with either a heat and material balanced plant case, a rigorous computer solution of a plant case, or computer solution of a design case. Once the hand base case is established, alternate cases can be done by hand (or small computer having limited core) using the Smith-Brinkley Method. 

Since the middle of the 1990s, another computation method, direct simulation Monte Carlo (DSMC), has been employed in analysis of ultra-thin film gas lubrication problems [13-15]. DSMC is a particle-based simulation scheme suitable to treat rarefied gas flow problems. It was introduced by Bird [16] in the 1970s. It has been proven that a DSMC solution is an equivalent solution of the Boltzmann equation, and the method has been effectively used to solve gas flow problems in aerospace engineering. However, a disadvantageous feature of DSMC is heavy time consumption in computing, compared with the approach by solving the slip-flow or F-K models. This limits its application to two- or three-dimensional gas flow problems in microscale. In the... 

This chapter has provided an overview of the main issues for computing and computational methods to support this work. For the past decade or so, the main limitations that have emerged are not in the amount or type of computational hardware that is available. The real issues are in providing a computational environment for informatics support and streamlining of the calculations. It is here that major efforts are still required to ensure effective integration of the methods and data generated into the drug discovery process. 

Synthetic constraints—such as difficulty, yield, management of starting materials, and intermediates—will naturally restrict the diversity of compounds that are made [7]. In silico designs with scaffolds that utilize similar synthetic steps will naturally be favored over those that are not. These pressures to make a small number of compounds with limited scaffold variability require computational methods to make exquisitely accurate predictions The... 

It is thus obvious that among numerous computational methods, first principles quantum chemical approach is indispensable. However, initially first principles quantum chemical calculations required the use of models consisting of a few atoms (clusters) and the range of properties was limited. Since the advent of modem computing resources, as well the models could be extended to cover larger variety of structures as the methodology has been... 

The key feature of the systems to be considered in this book is that they have short memories that is, the effects of perturbations diminish with the passage of time. In the example of this chapter, the carbon dioxide pressure returns to a value of 1 within a century or two of the perturbation, regardless of the size of the initial perturbation. In this kind of system, computational errors do not grow as the calculation proceeds instead, the system forgets old errors. That is why the reverse Euler method is useful despite its simplicity and limited accuracy. The many properties of the environment that are reasonably stable and predictable can, in principle, be described by equations with just this kind of stability, and these are the properties that can be simulated using the computational methods described in this book. 

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. 

---