Molecular dynamics studies of transmembrane proteins within complex lipid environments

Abstract

The interactions between lipids and proteins are crucial for many cellular processes. Typically, the nature of these interactions is studied in simple model lipid bilayers, which lack the complexity and heterogeneity of in vivo systems. Thus, this thesis investigates the impact of the lipid bilayer composition on protein dynamics and function. Both coarse grain and atomistic molecular dynamics simulations have been used to model membranes that contain lipid compositions approximating those found in vivo. The influence of these complex lipid environments on the dynamics of ?-helical and ?-barrel membrane protein is investigated. In particular, coarse grained simulations of a bilayer composed of a complex mixture of lipids, representing the Golgi apparatus, were used to identify preferential interactions of a helical transmembrane peptide with PIP2 lipids. Furthermore, atomistic molecular dynamics simulations have been used to identify several behaviour altering interactions between lipopolysaccharide, which is a key component of the Gram-negative bacterial outer membrane, and two outer membrane proteins, Hia and FecA. Lastly, coarse grained unilamellar vesicles, containing a complex mixture of phospholipids, were simulated in order to investigate protein aggregation and the short-term anomalous diffusion of lipids.

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ORCID for Syma Khalid: orcid.org/0000-0002-3694-5044

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