Future Perspectives

Future Perspectives

Molecular mechanics or force field was first introduced apparently independently by Hill and by Westheimer in 1949, primarily applied to organic chemistry to estimate properties such as strain energies among others. The functional form of the force field, focused in this article applied to biological systems, was established by Lifson in the 1960s. For over a half century, force fields have served us well, providing useful insights into and interpretation of biomolecular structure and function. Undoubtedly, it will continue to be widely used, thanks to its computational efficiency, while its reliability will continue to be improved. Yet, there are many well-known deficiencies as noted above. In addition, the number of energy terms used in a given force field cannot be uniquely determined and a highly redundant number of degrees of freedom are typically used. Consequently, the "parameters" in different force fields can be vastly different. Of course, the emphasis to incorporate polarization into the standard pair-wise potentials can be very useful; however, there is no unique way of treating polarization in molecular mechanics because it is of quantum mechanical origin Furthermore, often we are more interested in the properties derived from the dynamic dependence of the force field itself on molecular fluctuations.
One possibility is that the future development of force field ought to move beyond the current molecular mechanics approach, by using quantum mechanics explicitly to construct the force field. A number of the "polarizable force fields" listed below, such as density fitting and bond-polarization, already included some of the key ingredients towards this goal. The explicit polarization (X-Pol) method appears to have established the fundamental theoretical framework for a quantal force field; the next step is to develop the necessary parameters to achieve more accurate results than classical mechanics can offe