Elongation factor of SPT5 is known to be associated with RNA Polymerase II during the elongation stage of transcription. While its function is not fully understood, the structural studies suggest that SPT5 interacts with nucleic acids and may affect the stability of DNA and RNA exit sites. In this study, we present molecular dynamics simulations of SPT5 domains, KOW1 and KOW4, to investigate their interactions with DNA and RNA, respectively. We performed simulations with three different forcefields that are CHARMMc36m, AMBER ff14sb and AMBER ff19sb. Most of the protein-nucleic acid interactions were retained with the simulations using CHARMMc36m and AMBER ff19sb while AMBER ff14sb simulations resulted in losing some of the interaction sites and forming new interactions. CHARMMc36m provided a large fluctuation in RMSF values for DNA chains while AMBER force fields substantially decreased RMSF fluctuations and provided lower RMSD values. This suggests that AMBER forcefields may cause a higher stabilization of the base pair interactions comparing to CHARMMc36m. The additional simulations with CHARMMc36m for the complete elongation complex showed that the DNA chain fluctuations were decreased significantly comparing to the simulations of isolated KOW1 domain with DNA. This suggests that the DNA stabilization in the complete complex is achieved by a network of interactions rather than by interactions with only SPT5 domains that are directly interacting with DNA.

Exploring the protein-nucleic acid interactions for RNA polymerase II elongation factors with molecular dynamics simulations

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.