On the convergence of the conformational sampling in molecular dynamics simulations of membrane proteins
Topic:  8E Molecular Dynamics ;  1H Membrane Proteins
José D. Faraldo-Gómez¹, Lucy R. Forrest², Marc Baaden³, Peter J. Bond⁴, Carmen Domene⁴, George Patargias⁴, Jonathan Cuthbertson⁴, Mark S. P. Sansom⁴.
¹Weill Medical College of Cornell University, New York, NY, USA, ²Columbia University, New York, NY, USA, ³Centre National de la Recherche Scientifique, Paris, France, ⁴University of Oxford, Oxford, United Kingdom.
Presentation Number: 734-Pos
Poster Board Number: B573
A quantitative analysis of the convergence of the conformational sampling in molecular dynamics simulations of membrane proteins of duration in the order of 10 nanoseconds is presented. A set of proteins of diverse size and topology is considered, ranging from helical pores such as gramicidin and small-barrels such as OmpA, to larger and more complex structures such as rhodopsin and FepA. Principal Component analysis of the C-alpha-trace trajectories was used to assess the convergence of the conformational sampling in both the transmembrane domains and the whole proteins, while the time-dependence of the average structure was analyzed in order to obtain single-domain information. The membrane-spanning regions, particularly those of small or structurally simple proteins, were found to achieve reasonable convergence. By contrast, extra-membranous domains lacking secondary structure are often markedly under-sampled, exhibiting a continuous structural drift. This drift results in a significant imprecision in the calculated B-factors, which detracts from any quantitative comparison to experimental data. In view of such limitations, we suggest that similar analyses may be valuable in simulation studies of membrane protein dynamics, in order to attach a level of confidence to any biologically relevant observations.