The hyperthermostable protein rubredoxin from Pyrococcus furiosus is a 53-residue protein with a three-stranded antiparallel beta-sheet and several loops. In this paper, the hydrophobic interaction of residues on the surface of the protein was investigated as well as electrostatic interactions between residues. To investigate the effect of changes of electrostatic and hydrophobic interactions on the structure and the dynamic property of P. furiosus rebredoxin, molecular dynamics simulations in solution were performed on three mesophilic rubredoxins, P. furiosus rubredoxin, and five mutants of P. furiosus rubredoxin. Glu 14 of P. furiosus has a backbone hydrogen bond with N-terminal and multiple electrostatic interactions with Ala 1, Trp 3, and Phe 29. The multiple electrostatic interactions make the residues around the N-terminal stable, and the hydrogen bond between Glu 14 and Ala 1 remains even at high temperature. The flexibility of a loop from Asp 15 to Gly 26 is reduced by making the loop closer to the main part of rubredoxin by virtue of the multiple electrostatic interactions of Glu 14. In the middle of the beta-sheet. three hydrophobic residues, Val 4, Ile 11, and Leu 51, make the cluster binding the three strands of the beta-sheet. This cluster aggregates tightly to stabilize the beta-sheet and furthermore the whole protein. These interactions are considered to be important in maintaining the hyperthermostability.