This report describes the preliminary investigation, undertaken in the first year of my PhD studies, of the application of Density Functional Theory (DFT) calculations to biological systems. The CASTEP and CETEP codes have been used to perform calculations on a series of molecules in order to validate their use in modeling such systems. Although these codes were originally developed with periodic systems in mind the use of supercells has enabled individual molecules to be modelled with some measure of success.
Until recently the use of molecular modeling in the biological sciences has been restricted to semi-empirical classical and quantum mechanical techniques. This is due to the scale of most interesting biological systems which contain hundreds and often thousands of atoms. Such system sizes have been unachievable for ab initio techniques due to the prohibitive computational cost. The development of the plane-wave pseudopotential method and direct minimisation approaches to DFT calculations has lead to unprecedented gains in efficiency enabling calculations on several hundred atoms to be performed for the first time.
The use of ab initio techniques offers a wealth of opportunities within the biological sciences. While semi-empirical techniques have proved adequate for examining orientational problems such as the lock and key model of drug interaction, they lack the ability to model mechanisms at the electronic level with a reasonable degree of confidence in the results. A first-principles quantum mechanical solution of these problems enables questions regarding these mechanisms to be answered and offers a high degree of transferability between problems.
Having successfully validated the use of these techniques such questions will be approached in a system of interest in pharmacology. An outline of the intended investigation into Cytochrome P450 is given in Section 5.