MODELING OF THE TRANSITION-TEMPERATURE FOR THE HELICAL DENATURATION OF ALPHA-KERATIN INTERMEDIATE FILAMENTS

Simulations of the stability of the secondary and ternary structure of the alpha-keratin intermediate filament (IF) monomeric unit of wool a re reported. Based on the assumed secondary structure three segments o f the primary structure were selected: 1A, L12, and a part of 2B. Star ting with an ideal alpha-helical conformation for each IF-segment, mol ecular dynamics simulations were carried out on the atomistic level at various temperatures in vacuum using the CFF91 force field. In either simulation the expected destabilization of the helical structure with increasing simulation temperature was observed. By use of different p rocedures of analysis, transition temperatures for the alpha-helical d enaturation were determined that are significantly higher for the supp osedly alpha-helical segments 1A and 2B than for the linker segment L1 2. The different stabilities of segments 1A and L12 were further verif ied through simulations in water environment that show the linker segm ent to be non-helical at room temperature. The lower transition temper ature of segment L12 confirms the expectation that its amino acid sequ ence leads to increased conformational flexibility. The mobility of th e water molecules surrounding the IF-segment is found to be significan tly decreased by protein/water interactions.