The conformational dynamics of xylanase A from Streptomyces lividans (Sl-XlnA) were studied using Molecular Dynamics (MD) simulation to identify the thermally sensitive regions. Sl-XlnA begins to unfold at loop4 and this unfolding expands to the loops near the N-terminus. The high flexibility of loop6 during the 300 K simulation is related to its function. The intense movements of the 310-helices also affect the structural stability. The interaction between the α4β5-loop and the neighboring α5β6-loop plays a crucial role in stabilizing the region from the α4β5-loop to α6. The most thermally sensitive region is from β3 to loop4. The high mobility of the long loop4 easily transfers to the adjacent β4 and α4 and causes β4 and α4 to fluctuate. And, salt bridges ASP124-ARG79, ASP200-ARG159, and ASP231-LYS166 formed a “clamp” to stabilize the region including α4, β4, β5, β6, and β7. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 594–604, 2013.