Ribonuclease A adsorption onto charged self-assembled monolayers: A multiscale simulation study

Abstract

An ordered adsorption orientation is significant for the catalytic activity of immobilized enzymes. In this study, the orientations and conformation of ribonuclease A (RNase A) adsorbed on oppositely charged self-assembled monolayers (SAM) have been studied by a multiscale approach, including parallel tempering Monte Carlo, all-atom molecular dynamics and coarse-grained molecular dynamics simulations. Simulation results show that RNase A adsorbed on oppositely charged surfaces with opposite orientations. The active site of RNase A is oriented toward the surface when it adsorbs on a negatively charged surface; while for RNase A adsorbed on a positively charged surface, the active site is oriented toward the solution. Negatively charged surfaces could be used for RNase A removal since the catalytic active site is blocked. To bring the enzymatic catalysis of RNase A into play, positively charged surfaces can be used to control the orientation of RNase A with the active site accessible. The dipole moment and side chains of RNase A on both surfaces are slightly changed, whereas the backbone structure of RNase A is well preserved. That is to say, RNase A preserves its native conformation during the adsorption process. The simulation results could be applied into the design and development of substrates for the immobilization of ribonuclease A.