Binding of small molecule inhibitors to RNA polymerase-Spt5 complex impacts RNA and DNA stability.

Spt5 is an elongation factor that associates with RNA polymerase II (Pol II) during transcription and has important functions in promoter-proximal pausing and elongation processivity. Spt5 was also recognized for its roles in the transcription of expanded-repeat genes that are related to neurodegenerative diseases. Recently, a set of Spt5-Pol II small molecule inhibitors (SPIs) were reported, which selectively inhibit mutant huntingtin gene transcription.

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 to the elongation stage of the transcription process. In this work, we studied the elongation factor SPT5 and explored the 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.