The human p8(MTCP1) protein is constituted by an original disulfide bridged alpha-hairpin motif, and a third hydrophilic helix that appeared mobile and independent in NMR analysis. To get atomic scale description of the possible motions involved, a 12-ns molecular dynamics simulation of the C12A-p8(MTCP1) mutated protein and 10 400-ps simulations were performed in explicit water at 298 K. Analyses of the essential dynamics subspace and of the time-evolution of secondary structures indicate large displacements and internal motions of the third helix. Simulated order parameters, S,(2) are consistent to those obtained from (15)N-NMR relaxation data recorded at five different magnetic fields (proton resonance frequencies: 400, 500, 600, 700, and 800 MHz). The simulations show a fairly rigid alpha-hairpin motif with only very small local conformational changes, although the loop between helices undergoes significant correlated motions. The displacements and internal motions of the third helix can be essentially accounted for by alpha-helical to 3(10)-helical transitions near its N-terminus and by a hinge-bending motion near glycine 52. The loss of the alpha-helical conformation for a large part of the third helix during about 25% of the simulation time supports the possible occurrence of a slow motion as suggested by previous analyses of the (3)J(NH-H(alpha)) coupling constant values and of the proton-deuterium NH exchange kinetics.