Dimer formation is believed to have a substantial impact on regulating K-Ras function. However, the evidence for dimerization and the molecular details of the process are scant. In this study, we characterize a K-Ras pseudo-C-2-symmetric dimerization interface involving the effector interacting beta 2-strand. We used structure matching and all-atom molecular dynamics (MD) simulations to predict, refine, and investigate the stability of this interface. Our MD simulation suggested that the beta 2-dimer is potentially stable and remains relatively close to its initial conformation due to the presence of a number of hydrogen bonds, ionic salt bridges, and other favorable interactions. We carried out potential of mean force calculations to determine the relative binding strength of the interface, The results of these calculations indicated that the beta 2 dimerization interface provides a weak binding free energy in solution and a dissociation, constant that is close to 1 mM. Analyses of Brownian dynamics simulations suggested an association rate k(on) approximate to 10(5)-10(6) M-1 s(-1). Combining these observations with available literature data, we propose that formation of auto-inhibited beta 2 K-Ras dimers is possible but its fraction in cells is likely very small under normal physiologic conditions.