Analysis of Debye Waller factor and molecular dynamics simulation of Seryl tRNA synthetase

Department of Chemistry, University of Kalyani, Kalyani-741 235, Nadia, West Bengal, India E-mail : nilashisnandi@yahoo.com Fax : 91-33-25828282 Manuscript received online 06 October 2013, revised 29 November 2013, accepted 06 January 2014 Aminoacyl tRNA synthetases are enzymes responsible for first step of protein synthesis. We studied the Debye Waller factor (B-factor) of Seryl tRNA synthetase (SerRS) and carried out classical molecular dynamics simulation of SerRS in the present paper. The objective is to study the dynamics of SerRS through the course of conformational changes in its catalytic cycle. We observed from B-factor analysis and MD result that the N terminal domain is more ordered upon tRNA binding. Notably, the tRNA binding also impart influence on the catalytic domain as well. This conclusion is based on our simulated result on SerRS in Methanopyrus kandleri. Substrate binding organizes the catalytic domain as expected. The effect of substrate is noted in the serine ordering loop (SOL) region. An ordering of the closed state upon substrate binding is noted and is suggestive of an opening-closing motion. The connecting loop is most disordered in the closed state. The conformation of the loop changes relative to the initial structure upon substrate binding. This indicates a domain organization and is suggestive of a communication between domains upon substrate binding. This is concluded based on the fact that the tRNA is not directly linked with connecting loop or the catalytic domain throughout the course of simulation. The effect of tRNA on the catalytic core is most dramatic in the motif 2 region. The motif 2 exhibit least conformational fluctuation, even in the open state, when tRNA is absent. This indicates that tRNA has long ranged electrostatic interaction with the catalytic domain. A hinge movement around an axis nearly parallel to H4 is found in the present study. The tRNA is responsible for this hinge type movement. The domains move in a hinge motion in the absence of tRNA (both in open state with tRNA and open state without tRNA). It is most important to note that the hinge movements of domains occur in opposite ways in the absence of tRNA in open state and in the absence of tRNA in closed state. This is evident from the change of the sign of the dihedral angle in the two cases. Clearly, the hinge motion brings the CCA terminal tRNA closer to the catalytic core which is essential for the reaction. We studied the dynamics of various conserved active site residues in the open and closed states. The active site residues are more ordered in the closed state compared to the open state and this result corroborates the Bfactor results described earlier. The MD simulation result indicate important catalytic role of residues in motif 2 loop. Interesting influence of Zn2+ ion is observed in the Ser binding site. The paper presents the first study of SerRS dynamics and reveals various conformational changes hitherto unobserved