Molecular dynamics simulations of biomolecules: membranes, peptides and multidrug efflux transporters

Molecular dynamics (MD) is a technique that involves computational simulations of physical movement of atoms from a single lipid molecule to complex biological protein-membrane mimetic systems. With the fast advancing in computing power in recent years, bigger, more detailed and complex systems are allowed to perform on a much longer timescale. The interactions between proteins, ions and lipids inside a cell are vital for its function. Thus, this thesis focuses on investigating protein dynamics and functions in different lipid bilayer environment and system compositions. Coarse-grained and atomistic molecular dynamics simulations have been used to model biological systems both in bacterial and mammalian cells. The impact of lipid environment on the orientation of a short ?-helical peptide, the fukutin transmembrane domain, from the protein fukutin, which is located in the Golgi membrane, is investigated. In particular, coarse-grained simulations are used to probe the tilt angle and oligomerisation state of fukutin transmembrane domain in different types of lipid bilayers. Furthermore, atomistic molecular dynamics simulations were used to identify interactions between the dimer formed from two fukutin transmembrane domains. The Multidrug and Toxic compound Extrusion (MATE) transporter are simulated in atomistic detail to identify the importance of protein-ion interactions, which plays a key role in its conformational change leading to substrate/drug extrusion from the bacteria inner membrane. Lastly, a novel method called inverted-topology repeats method is employed to construct an inward-facing model of a MATE transporter from the X-ray crystal structure of NorM_VC