Title:	Molecular Modeling of Lipid Membranes
DNr:	SNIC 2015/1-272
Project Type:	SNIC Medium Compute
Principal Investigator:	Arnold Maliniak <arnold.maliniak@mmk.su.se>
Affiliation:	Stockholms universitet
Duration:	2015-08-28 – 2016-09-01
Classification:	10402 10603 10602
Homepage:	http://www.su.se/profiles/arnold
Keywords:

Abstract

The project presented in this application consists of molecular modeling of soft biological matter in general and lipid membranes in particular. Two main topics can be identified in this project: i) Interactions of biomolecules with lipid membranes, and ii) molecular properties and phase polymorphism in membrane models. We investigate interactions of model membranes with various bioactive molecules such as carbohydrates, peptides and anaesthetics. In addition, we study how the lipid composition and molecular properties of the lipids (ionic/zwitterionic, saturated/unsaturated), influence the polymorphism in membranes. Our studies range from investigations of the local structure in the polar headgroup of the lipid to mechanic properties of bilayers. Recently, we have studied interactions of trehalose with a lipid bilayer, using molecular dynamics (MD) computer simulations. Trehalose is a disaccharide that occurs naturally in insects, plants, fungi, and bacteria. One of the fascinating aspects of trehalose is its presence in various organisms that can survive at the extremes of temperature and dehydration. It is so, because the trehalose exhibits protein and membrane stabilizing capability. However the essential question of whether trehalose is bound or expelled from membrane surfaces remains unsolved and prevents a molecular understanding of stabilizing mechanisms. We described the bilayer-trehalose interactions using a simple analytical two site model, which was in good agreement with the MD results. In addition we found a very good agreement with recently suggested models based on SANS and thermodynamic experiments. In this study it was hypothesised that the mechanism for the interaction and the membrane properties exhibit a drastic dependence on the sugar concentration. Furthermore, we observed a drastic increase of the lateral order in the lipid bilayer, resulting in a significant reduction of the translational diffusion. We ascribe these results to the formation of a glassy state, as suggested in earlier experimental studies. We use our atomistic MD trajectories to construct coarse-grained (CG) bilayer-carbohydrate interaction potentials. To that end a recently proposed method for construction of CG potentials is employed (JCTC, 2013, 9, 1512-1520). Coarse-graining is a significant step in the effort to reach larger system sizes and longer timescales, and proceeds to that goal by reduction of atomic details in the interaction model. Atomic details are therefore sacrificed for increased simulation speed of several orders of magnitude. We will subsequently carry out CGMD simulations to access significantly longer time scales (associated with the formation of the glassy state) for bilayer-trehalose interactions. In particular we will investigate elastic properties of the membrane (such as area compressibility and bending moduli), which require long time trajectories.