Kornberg devoted two decades to the development of methods to visualize the atomic structure of RNA polymerase and its associated protein components. Initially, Kornberg took advantage of expertise with lipid membranes gained from his graduate studies to devise a technique for the formation of two-dimensional protein crystals on lipid bilayers. These 2D crystals could then be analyzed using electron microscopy to derive low-resolution images of the protein's structure. Eventually, Kornberg was able to use X-ray crystallography to solve the 3-dimensional structure of RNA polymerase at atomic resolution. Through these studies, Kornberg created an actual picture of how transcription works at a molecular level. According to the Nobel Prize committee, "the truly revolutionary aspect of the picture Kornberg has created is that it captures the process of transcription in full flow. What we see is an RNA-strand being constructed, and hence the exact positions of the DNA, polymerase and RNA during this process.” With P Cramer , D A Bushnell, J Fu, A L Gnatt, B Maier-Davis, N E Thompson, R R Burgess, A M Edwards, P R David. Digital facsimile from PubMedCentral at this link.

In 2006 Kornberg was awarded the Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription."