Monday, September 8, 2014

Making good on my "Open Access" pledge

My most recent paper has just been published in PeerJ . It was a LONG time in the making, to the point that my 12-yo daughter once told me (only half-in-jest), that I should "cut my losses and forget about it". I am quite happy about how it turned out: besides describing an analysis of a reaction mechanism and the influence of the redox state of a hard-to-converge Fe-S cluster , it also contains  the first computations including the weighed contributions of 1.2*1013 protonations states of a protein on the reaction it catalyzes. The computational approach described here is relatively simple to perform provided that one has a good estimate of the relative abundances of those protonation states, which can be obtained through Monte Carlo sampling  once the site-site interactions have been computed with a Poisson-Boltzmann solver. To my mind, this is clearly superior to the usual approach of considering only  the "most likely" protonation state (which may often not be the state with the most significant influence on the electrostatic field surrounding the active site). What do you think of it?

Programs needed to use this approach:
MCRP, by Baptista et al., ITQB, Lisbon
MEAD, by Don Bashford, currently at St. Jude Children's research hospital
Any molecular mechanics code, to compute the change of the total electrostatic energy as each individual amino acid is protonated/deprotonated