Molecular Dynamics Simulations Of L1 Ligase Ribozyme

L1 ligase ribozyme is not only an important evidence to support the hypothesis that the life originates from "RNA World", but also the template as the new tool enzymes and ribozyme drugs. In this article the L1 ligase ribozyme was studied based on molecular dynamics simulations. It helped us to understand the conformational transition mechanism of the ribozyme, and provided a theoretical expression for the application of the ribozyme.The crystal structure of L1 ligase ribozyme was obtained from the PDB database, and the ribozyme was simulated based on molecular dynamics by using the Amber software, at the same time, the pathways between the active and inactive conformations and the related factors were studied. The research found that x torsion angle of U38 base performed the preferred conformation, known as trans conformation, in the dynamic equilibrium when the initial angle was between the-26.058 and -180 degrees or between 79.989 and+180 degrees. The Mg ion which located in the 72nd position took an important role in maintaining the conformation of Gl, U38 and A51 which located in active cite of Q conformation. At the same time the H2O molecule, located in the 86th position, emerged synergistic action with the Mg ion in maintaining this active conformantion. Our research also found that seven virtual torsion anglesη3g,η39,θ17,θ18θ37,θ44 andθ45 took an important role in conformation transitions, which followed the different pathways. When the conformation transformed from P toη39 had some changes throughout the transition process, andθ17 andθ44 performed a significant change in the early stage, then in the medium termθ18 fluctuated obviously, while four virtual dihedral anglesθ37,η38,θ44 andθ45 contributed to the conformational changes at a late stage. When the conformation transformed from P to Q,η39 had some changes throughout the transition process, andθ7 andθ44 performed an significant change in the early stage, then in the medium termθ18 fluctuated obviously, while four virtual dihedral anglesθ37,η38,θ44 andθ45 contributed to the conformational changes at the late stage. However, when Q was transformed to P, onlyη39 changed a little, whileθ37 andθ44 contributed to the whole transition process. On one hand,θ17θ18 andη38 had a significant impact on this transition in the initial stage, on the other hand three dihedral anglesθ17,θ18,θ45 made outstanding contributions in the final stage. The study also found U38 and G44 bases formed varieties of hydrogen bonds with other bases, but these hydrogen bonds maintained very short time. The main reason was that the two bases had not formed base pair with other bases during the period of conformation transition, at the same time, the base stacking around U38 and G44 was very weak.