THE VOLUME OF ATOMS ON THE PROTEIN SURFACE - CALCULATED FROM SIMULATION, USING VORONOI POLYHEDRA

We analyze the volume of atoms on the protein surface during a molecul ar-dynamics simulation of a small protein (pancreatic trypsin inhibito r). To calculate volumes, we use a particular geometric construction, called Voronoi polyhedra, that divides the total volume of the simulat ion box amongst the atoms, rendering them relatively larger or smaller depending on how tightly they are packed. We find that most of the at oms on the protein surface are larger than those buried in the core (b y similar to 6%), except for the charged atoms, which decrease in size , presumably due to electroconstriction. We also find that water molec ules are larger near apolar atoms on the protein surface and smaller n ear charged atoms, in comparison to ''bulk'' water molecules far from the protein. Taken together, these findings necessarily imply that apo lar atoms on the protein surface and their associated water molecules are less tightly packed (than corresponding atoms in the protein core and bulk water) and the opposite is the case for charged atoms. This l ooser apolar packing and tighter charged packing fundamentally reflect s protein-water distances that are larger or smaller than those expect ed from van der Waals radii. In addition to the calculation of mean vo lumes, simulations allow us to investigate the volume fluctuations and hence compressibilities of the protein and solvent atoms. The relativ ely large volume fluctuations of atoms at the protein-water interface indicates that they have a more variable packing than corresponding at oms in the protein core or in bulk water. We try to adhere to traditio nal conventions throughout our calculations. Nevertheless, we are awar e of and discuss three complexities that significantly qualify our cal culations: the positioning of the dividing plane between atoms, the pr oblem of vertex error, and the choice of atom radii. In particular, ou r results highlight how poor a ''compromise'' the commonly accepted va lue of 1.4 Angstrom is for the radius of a water molecule.