Normal mode analysis of membrane protein dynamics using the vibrational subsystem analysis

Abstract

The vibrational subsystem analysis is a useful approach that allows for evaluating the spectrum of modes of a given system by integrating out the degrees of freedom accessible to the environment. The approach could be utilized for exploring the collective dynamics of a membrane protein (system) coupled to the lipid bilayer (environment). However, the application to membrane proteins is limited due to high computational costs of modeling a sufficiently large membrane environment unbiased by end effects, which drastically increases the size of the investigated system. We derived a recursive formula for calculating the reduced Hessian of a membrane protein embedded in a lipid bilayer by decomposing the membrane into concentric cylindrical domains with the protein located at the center. The approach allows for the design of a time- and memory-efficient algorithm and a mathematical understanding of the convergence of the reduced Hessian with respect to increasing membrane sizes. The application to the archaeal aspartate transporter GltPh illustrates its utility and efficiency in capturing the transporter's elevator-like movement during its transition between outward-facing and inward-facing states.