Framework for Martini-based Coarse-grained Model of Enzymes: Model Development and Experimental Validation

Recent experiments have shown that enzyme activity can preserved in harsh environments by complexing enzyme with polymer into a Protein-Polymer Hybrid (PPH). In a successful PPH, heteropolymer strands bind to the enzyme surface and restrain the folded protein without adversely affecting the binding and active sites. It is believed that hybridization is driven by non-covalent interactions at the enzyme surface including hydrophobicity and electrostatics. Molecular modeling of these interactions is not practical at the all-atom scale due to the long timescales and large particle counts needed to characterize binding. Protein structure at the scale of amino acid residues is parsimoniously represented by a coarse-grained model in which one particle represents several atoms, significantly reducing the cost of simulation. In this study we present two coarse-grained enzyme models - lipase and dehalogenase - prepared using a top-down modeling strategy. We simulate each enzyme in aqueous solution and calculate statistics of protein surface features and shape descriptors. The values from the coarse-grained data are compared with the same calculations performed on all-atom reference systems, revealing key similarities of surface chemistry at the two scales. Structural measures are calculated from the all-atom reference systems and compared with estimates from small-angle X-ray scattering (SAXS) experiments, with good agreement between the two. The described procedures of modeling and analysis comprise a framework for the development of coarse-grained models of protein surfaces with validation to experiment.