“Do not go where the path may lead, go instead where there is no path and leave a trail. Ralph Waldo Emerson” Paraphrasing Ralph Waldo Emerson, a 19th century New England philosopher and essayist, I shall try to show in this lecture how I have gone where there was no path and left a trail. It leads from trajectory studies of the reactions of small molecules to molecular dynamics simulations of macromolecules of biological interest. In developing computational methods to study complex chemical systems, the essential element has been to introduce classical concepts wherever possible, to replace the much more time-consuming quantum mechanical calculations. In 1929 Paul Dirac (Nobel Prize in Physics, 1933) wrote (Figure 1) the now familiar statement: “The underlying