Most computational studies of biologically relevant systems have used
Molecular Mechanics (MM). While MM is generally reliable for many applications,
chemical reactions and bond formations/breakage are not describable in MM. In
contrast, Quantum Mechanics (QM) is an approach that utilizes wave functions and/or
electron density functions for property and structural analyses and hence does not
suffer from such limitations. QM methods can be classified into two main frameworks,
ab initio and semi-empirical. Semi-empirical methods utilize experimental or ab initio
results to make additional approximations, thereby using a combination of some ab
initio calculations and fitted experimental data. Despite the accuracy and general
applicability of QM, the major disadvantages are limitations due to the system size. Not
surprisingly, hybrid methods that partition the problem at hand into subsystems have
been developed. Some of these methods mix QM with MM, and others are strictly QM,
but limit the range of interactions. As a result, there exists a plethora of methods, some
with fanatical followers, with the result that researchers are often faced with
bewildering choices.
This review, perhaps more accurately described as a mini-review or perspective,
examines recent calculations on biologically relevant (including biomimetic molecules)
in which QM is necessary, to a greater or lesser degree, to obtain results that are
consistent with the experiment. The review is not an exposition on the theoretical
foundations of different methods, but rather a practical guide for the researcher with an
interest in using computational methods to produce biologically, or at least
biochemically, useful results. Because of our own specific interests, the Arg-Gly-Asp
sequence, or so-called RGD, figures prominently in the work, in terms of size,
including oligomers of RGD, and strengths of interactions. A key feature of RGD is its
role in the binding of cells to the Extra Cellular Matrix (ECM) depending on the cell
type and receptor protein on the cell itself. The ECM is comprised of spectra of
biological compounds such as proteoglycans and fibrous proteins; RGD is located and
found as a motif on these fibrous proteins. The cell bindings to the ECM are done via
integrin-RGD binding. Because metal interactions and hydrogen bonding significantly
affect integrin-RGD binding, theoretical methodology beyond MM is needed. IntegrinRGD binding affects the adhesion and movement of cells along the ECM. Hence, these
interactions are highly relevant to understanding the spread of cancer in an organism.
Keywords: Molecular mechanics (MM), Quantum mechanics (QM), Neurooncolgy, Glycobiology, Extra cellular matrix (ECM).
