2.
I'm struck by how small the improvements in R/Rfree are in Diederichs & Karplus (ActaD 2013, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689524/); the authors don't discuss it, but what's current thinking on how to estimate the expected variation in R/Rfree - does the Tickle formalism (1998) still apply for ML with very weak data?