Development of Native-Based Dissipative Particle Dynamics Framework for Modeling Lysozyme

Conjugating enzymes with copolymer bottlebrushes has been recently shown to increase structural stability and enhance activity of enzymes at high temperatures. Herein we develop a first native-based approach to simulate dynamics of lysozyme using dissipative particle dynamics (DPD) simulations. DPD is a mesoscale approach that utilizes soft repulsive interactions, thus permitting the use of a significantly larger time step between successive iterations. The native contact map obtained from the crystal structure and structural characterizations from our molecular dynamics (MD) simulations are used to optimize DPD parameters to model lysozyme. We focus on developing an algorithm to assign the interactions between the enzyme’s beads based on native contact pairs to achieve a closest match between the DPD and MD structural characteristics. Using our approach, all six right-handed helical segments in lysozyme are reproduced in DPD simulations and can be located on the time-averaged contact map calculated from DPD simulations. Radius of gyration is also closely matched in DPD simulations to that obtained from atomistic trajectory. Further development of this framework could allow one to model a variety of larger systems incorporating enzymes and polymer chains.