Coarse-grain simulations on NMR conformational ensembles highlight non catalytic functional residues in proteins

Abstract

Dynamics are a key feature of protein function, and this is especially true of gating residues, which occupy cavity or tunnel lining positions in the protein structure, and will reversibly switch between open and closed conformations in order to control the diffusion of small molecules within a proteins internal matrix. Earlier work on globins and hydrogenases have shown that these gating residues can be detected using a multiscale scheme combining all atom classic molecular dynamics simulations and coarse grain calculations of the resulting conformational ensemble mechanical properties. Here we show that the structural variations observed in the conformational ensembles produced by NMR spectroscopy are sufficient to induce noticeable mechanical changes in a protein, which in turn can be used to identify residues important for function and forming a mechanical nucleus in the protein core. This new approach, which combines experimental data and rapid coarse-grain calculations and no longer needs to resort to time-consuming all-atom simulations, was successfully applied to five different protein families. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/532507v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@104c511org.highwire.dtl.DTLVardef@25ebecorg.highwire.dtl.DTLVardef@1a3d721org.highwire.dtl.DTLVardef@180f1d0_HPS_FORMAT_FIGEXP M_FIG C_FIG