In silico study of the interaction of the Myelin Basic Protein C-terminal a-helical peptide with DMPC and mixed DMPC/DMPE lipid bilayers

Biological membranes continue to be extensively investigated in different ways. This paper presents the benefits of Molecular Dynamics (MD) approaches to study the properties of biological membranes and proteins using the freely available GROMACS package, in the context of the Myelin Basic Protein (MBP) C-terminal a-helical peptide. A mixed membrane consisting of 2-Dimyristoyl-sn-Glycero-3-phosphocholine/1,2-Dimyristoyl-sn-Glycero-3- phosphoethanolamine (DMPC/DMPE), and pure DMPC membranes, composed of 188 and 248 lipids, respectively, were simulated for 200 ns at 309 K. The DMPC membrane was approximately three times more fluid compared to the DMPC/DMPE system, with the diffusion coefficients (D) being 0.0207x10-5 cm2/s and 0.0068x10-5 cm2/s, respectively. In addition, the 14-residue peptide representing the C-terminal a-helical region of murine Myelin Basic Protein (MBP), with amino acid sequence NH2-A141YDAQGTLSKIFKL154-COOH , was simulated in both membrane systems for 200 ns. The peptide penetrated further into the DMPC bilayer compared to the mixed DMPC/DMPE bilayer, potentially because of the reduced accessibility of the charged peptide amino acid side chains to the formal positive charge of the amine N atom surrounded by methyl and methylene groups in DMPC, that might have resulted in greater overall peptide mobility [3]. These findings are significant in their implication that membrane composition affects the behavior of MBP, providing further insights into myelin structure. Our preliminary results suggest that local changes in membrane composition (e.g. enrichment in DMPE molecules), as well as, electrostatic nature of primary amino acid sequence could cause localized denaturation / instability of external MBP a-helices possibly augmenting the degradation of myelin in multiple sclerosis (MS), resulting in a subsequent decrease of nerve impulse propagation efficiency.