The development of computer simulations of the geometries and thermodynamics of biological molecules

The historical development of computer simulations of molecular geometry and thermodynamics (molecular mechanics, force field method) is outlined. The advantages and disadvantages of techniques such as energy minimization, molecular dynamics and free energy perturbation are discussed. An example is included that shows how energy minimization studies of dopamine D-2 antagonists have been used to develop an understanding of the three-dimensional pharmacophore necessary for this pharmacological activity.