Holy Grails for Computational Organic Chemistry and Biochemistry

Computational chemistry and biochemistry began with Isaac Newton's classical mechanics in the 17th century and the establishment of quantum mechanics in the 1920s. Enabled by extraordinary advances in computers, in the last half century, this field has become a robust partner with experiment. The challenges facing computational chemists and biochemists, the Holy Grails of the field, are described. These include the development of a highly accurate density functional, ideally one that has universal chemical accuracy, and accurate polarizable force fields, as well as methods to handle efficiently the massive number of computations that must be performed for molecular dynamics and for the computation of flexible systems such as proteins. We estimate when the breakthroughs that will make computation a powerful engine for chemical discovery and design will be achieved. The Holy Grails of this field involve methods to enable the accurate and efficient prediction of structures and properties of complex biological systems and materials. The principal Holy Grail is a routine computational method for the prediction and design of multicomponent, often heterogeneous, functional systems and devices.