A multibaric-multithermal molecular dynamics (MD) simulation of a 10-residue protein, chignolin, was performed. All-atom model with the Amber parm99SB force field was used for the protein and the TIP3P model was used for the explicit water molecules. This MD simulation covered wide ranges of temperature between 260 and 560 K and pressure between 0.1 and 600 MPa and sampled many conformations without getting trapped in local-minimum free-energy states. Folding events to the native β-hairpin structure occurred five times and unfolding events were observed four times. As the temperature and/or pressure increases, fraction of folded chignolin decreases. The partial molar enthalpy change ΔH and partial molar volume change ΔV of unfolding were calculated as ΔH = 24.1 ± 4.9 kJ/mol and ΔV = −5.6 ± 1.5 cm3/mol, respectively. These values agree well with recent experimental results. Illustrating typical local-minimum free-energy conformations, folding and unfolding pathways were revealed. When chignolin unfolds from the β-hairpin structure, only the C terminus or both C and N termini open first. It may undergo an α-helix or 310-helix structure and finally unfolds to the extended structure. Difference of the mechanism between temperature denaturation and pressure denaturation is also discussed. Temperature denaturation is caused by making the protein transferred to a higher entropy state and making it move around more with larger space. The reason for pressure denaturation is that water molecules approach the hydrophobic residues, which are not well hydrated at the folded state, and some hydrophobic contacts are broken. Proteins 2012;. © 2012 Wiley Periodicals, Inc.