Protein-Nucleic Acid Interactions for RNA Polymerase II Elongation Factors by Molecular Dynamics Simulations

RNA polymerase II (Pol II) forms a complex with elongation factors to proceed the elongation stage of the transcription process. In this work, we studied elongation factor SPT5 and explored protein nucleic acid interactions for the isolated systems of KOW1 and KOW4 domains of SPT5 with DNA and RNA, respectively. We performed molecular dynamics (MD) simulations using three commonly used force fields that are CHARMM c36m, AMBER ff14sb and ff19sb. These simulations showed that most of the protein-nucleic acid interactions in the native state were retained with an increased electrostatic binding free energy for all force fields used. RNA was found highly dynamic with all force fields while DNA had relatively more stable conformations with the AMBER force fields compared to CHARMM. Furthermore, we performed MD simulations of the complete elongation complex using CHARMM c36m force field to compare the dynamics and interactions in the isolated systems. Similar strong KOW1 and DNA interactions were observed in the complete elongation complex simulations and DNA was further stabilized by a network of interactions involving SPT5-KOW1, SPT4 and rpb2 of Pol II. Overall, our study showed that the accuracy of force fields and the presence of the entire interaction network are important for elucidating the dynamics of protein-nucleic acid systems.