Biophysics Electrostatic potential molecular surfaces ( nucleic acids / proteins / drug - nucleic acid interactions / protein - ligand interactions )

Color-coded computer graphics representations of the electrostatic potentials of trypsin, trypsin-inhibitor, prealbumin and its thyroxine complex, fragments of double-helical DNA, and a netropsin-DNA complex illustrate the electrostatic and topographic complementarity in macromolecule-ligand interactions. This approach is powerful in revealing intermolecular specificity and shows promise of having predictive value in drug design. The electrostatic potential is a powerful tool that has provided insights into intermolecular association and molecular properties of small molecules (1), actions of drug molecules and their analogs (2), the biological function of hemoglobin (3), and enzyme catalysis (4). We thought that, given the electrostatic potentials of both a ligand and its receptor, much greater progress might be made in the "rational design" of the optimal ligand (5-7). Subsequent studies of the electrostatic potentials of macromolecules (8-10) demonstrate the feasibility of this approach, but there has been no satisfactory way to represent the electrostatic potential in a way useful for understanding electrostatic complementarity. This problem is effectively solved by displaying the electrostatic potential molecular surface with a realtime interactive color graphics facility (11) using the molecular surface definition of Richards (12) and the algorithm developed by M. Connolly. *