Systematic multiscale simulation of membrane protein systems

Abstract

Current multiscale simulation approaches for membrane protein systems vary depending on their degree of connection to the underlying molecular scale interactions. Various approaches have been developed that include such information into coarse-grained models of both the membrane and the proteins. By contrast, other approaches employ parameterizations obtained from experimental data. Mesoscopic models operate at larger scales and have also been employed to examine membrane remodeling, protein inclusions, and ion channel gating. When bridged together such that molecular-level information is propagated between the different scales, a systematic multiscale methodology for membrane protein systems can be achieved.

Fig. 1

A schematic showing the multiscale simulation methodology for a membrane protein system. The specific example of N-BAR domain protein mediated membrane remodeling is considered, but this approach can in principle be applied to a wide variety of membrane protein systems. The three main scales of the multiscale methodology are the molecular (A), coarse-grained (CG) (B) and mesoscopic (C). These scales are bridged by paths (1-3). Paths (1) and (3) connects the molecular to the mesoscopic via the CG scale, while path (2) directly connects the molecular to the mesoscopic regime. The image in path (2) shows how the N-BAR protein is directly transformed into a mesoscopic spontaneous curvature field (red/purple border surrounding the liposome in the inset), which combines with the elastic membrane (the liposome in the inset). Path (3) instead first describes emergent mesoscopic behavior at the CG level and then employs it in the development of new mesoscopic models. This approach utilizing CG simulation provides a more refined level of detail in the final mesoscopic model than could be obtained along path (2). For example, the spatial correlations shown in the orange box can be employed to derive new phenomenological mesoscopic field based descriptions of the system that capture the behavior beyond what could be accessed with even very large scale MD simulation.