INTRINSIC COMPRESSIBILITY AND VOLUME COMPRESSION IN SOLVATED PROTEINSBY MOLECULAR-DYNAMICS SIMULATION AT HIGH-PRESSURE

Constant pressure and temperature molecular dynamics techniques have b een employed to investigate the changes in structure and volumes of tw o globular proteins, superoxide dismutase and lysozyme, under pressure . Compression (the relative changes in the proteins' volumes), compute d with the Voronoi technique, is closely related with the so-called pr otein intrinsic compressibility, estimated by sound velocity measureme nts. In particular, compression computed with Voronoi volumes predicts , in agreement with experimental estimates, a negative bound water con tribution to the apparent protein compression. While the use of van de r Waals and molecular volumes underestimates the intrinsic compressibi lities of proteins, Voronoi volumes produce results closer to experime ntal estimates. Remarkably, for two globular proteins of very differen t secondary structures, we compute identical (within statistical error ) protein intrinsic compressions, as predicted by recent experimental studies. Changes in the protein interatomic distances under compressio n are also investigated. It is found that, on average, short distances compress less than longer ones. This nonuniform contraction underline s the peculiar nature of the structural changes due to pressure in con trast with temperature effects, which instead produce spatially unifor m changes in proteins. The structural effects observed in the simulati ons at high pressure can explain protein compressibility measurements carried out by fluorimetric and hole burning techniques. Finally, the calculation of the proteins static structure factor shows significant shifts in the peaks at short wavenumber as pressure changes. These eff ects might provide an alternative way to obtain information concerning compressibilities of selected protein regions.