Protein diffusion and long-term adsorption states at charged solid surfaces

Understanding how proteins interact with surfaces is vital for designing functionalized materials. Prior studies have explored protein adsorption mechanisms, but the role of specific residues in anchoring proteins to surfaces remains unclear. While it is known that electrostatic interactions influence adsorption, the dynamic behavior of proteins post-adsorption is less understood. Recent work has identified Arg128 as a key residue in lysozyme adsorption to ionic surfaces. However, the transition between adsorption and diffusion states has not been fully characterized. Experimental observations suggest energy barriers for protein clustering, but the molecular-level mechanisms behind these barriers remain unresolved. This gap motivates the need for detailed simulations to track protein movement and orientation changes. No prior work has resolved how hydrogen bonds and water layers affect diffusion pathways. This uncertainty drove the use of atomistic simulations to explore desorption and diffusion processes. The study aims to bridge the gap between experimental findings and molecular-level explanations.

This study investigates the desorption and diffusion pathways of lysozyme on a charged surface using steered molecular dynamics simulations. The focus is on the role of Arg128 in anchoring and reorienting the protein. By simulating the movement of Arg128, the researchers aim to identify how protein orientation influences diffusion. The study also seeks to determine the energy barriers associated with diffusion and how hydrogen bonds contribute to these barriers. The goal is to understand the transition from adsorption to diffusion states. This approach allows for a detailed analysis of the protein's dynamic behavior. The findings could clarify how structured water layers and geometric constraints affect protein mobility. The study provides a framework for interpreting experimental observations of protein clustering.

The researchers employed fully atomistic steered molecular dynamics simulations to model lysozyme adsorption and diffusion. Simulations were initiated from pre-existing adsorption trajectories, focusing on Arg128 at the N,C-terminal face. The desorption process was simulated by pulling Arg128 away from the surface in the normal direction. After desorption, the protein was allowed to resorb, and its new orientation was recorded. Diffusion was then modeled by pulling Arg128 parallel to the surface. The simulations tracked hydrogen bond interactions and energy changes during these processes. Structured water layers at the surface were monitored for their influence on protein orientation. The energy barriers for diffusion were calculated based on hydrogen bond disruption. This approach enabled a detailed view of the protein's movement and reorientation.

The simulations revealed that Arg128's orientation is critical to lysozyme diffusion. Initially, Arg128 aligns normal to the surface during adsorption, but after resorption, it lies parallel to the surface. This reorientation is due to geometric constraints from structured water layers. The diffusion process from the resorbed state has a lower energy barrier of approximately 0.9 eV. This barrier is associated with breaking hydrogen bonds along the diffusion pathway. The calculated barrier aligns with experimental observations of lysozyme clustering. The study found that Arg128 cannot return to its original orientation post-resorption. The hydrogen bonds between the protein and surface are disrupted during diffusion. These findings suggest that protein diffusion is influenced by both electrostatic and geometric factors.

The study demonstrates that Arg128's orientation determines lysozyme diffusion on charged surfaces. The protein's reorientation post-resorption is constrained by water layers, leading to a new adsorption state. The energy barrier for diffusion is linked to hydrogen bond disruption. These results align with experimental observations of protein clustering. The findings highlight the importance of studying both adsorption and diffusion processes. The study provides insights into how electrostatic and geometric factors influence protein mobility. The results suggest that structured water layers play a key role in protein orientation. These conclusions support the need for detailed simulations to understand protein behavior on surfaces.