Brownian translocation and protein conformational dynamics of a mitochondrial RNA polymerase along DNA

In our recent computational study of human mitochondrial RNA polymerase (RNAP) or POLRMT, we illustrate collective variable (CV) refinement in conformational samplings, in the context of atomic molecular dynamics (MD) simulation and data learning. We performed extensive samplings along coupled or non-coupled translocation paths of POLRMT along DNA, with or without enforced fingers subdomain opening. We then employed time-lagged independent component analysis and comparatively the variational approach for Markov processes with neural network implementation for kinetic lumping or dimensional reduction on selected atomic coordinate sets for CVs, as well as for timescale prediction of the translocation. Our results suggest that POLRMT translocation is coupled with NTP binding to enable the subdomain opening, which hardly happens spontaneously otherwise. The POLRMT translocation mechanism thus appears to be a variation of Brownian ratcheting for an RNAP, biased or facilitated by NTP substrate binding.