Life Sciences & Biotechnology
Title : | Molecular Simulations of Membrane Bending by Proteins |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Taraknath Mandal, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | taraknath@iitk.ac.in |
Equipments : | Graphics processing unit (GPU) machine |
Details
Executive Summary : | Protein induced membrane bending or remodeling is essential for numerous cellular processes including cell division, cell growth, cell repair, organelle biogenesis, fertilization, viral infections, membrane targeting and tethering, protein activation and many others. Many of such biological processes are mediated by highly bent or curved membrane of radii of curvature as small as a few nanometer. There are specific class of proteins which supply persistent energy input for generating and maintaining membrane curvature which requires a substantial amount of energy to overcome the bending rigidity of the membrane. In spite significant experimental research performed in the last decades, understanding membrane remodeling process is often not clear in vivo as multiple proteins function together and each of them potentially use multiple mechanisms to drive the membrane bending process. Molecular simulations can be used to understand the roles of specific proteins and to identify the relative contribution of the individual components. In this project, we plan to employ multiscale molecular simulations (fully atomistic and coarse-grained) to investigate the ‘protein insertion’ (shallow insertion) and ‘protein-crowding’ mechanisms of membrane curvature generation. First, we shall study formation of functional membrane domains in model mixed lipid membranes which plays an important role in protein sensing and binding. Particular focus will be on understanding the effects of polar heads and saturation level of lipid tails on the membrane domains and to investigate if the membrane domains can change the spontaneous curvature of the membrane which is likely to induce membrane curvature to some extent. Next, we shall investigate the mechanisms by which the membrane domains sense and bind proteins – particularly, the role of hydrophobic interaction (amphipathic insertion) and electrostatic interactions (through charged residues) in protein binding. Special attempts will be made to understand why some class of proteins induce positive membrane curvature while the others generate negative curvature and if there is any correlation between the insertion depth of the protein motif and the nature (sign) of the membrane curvature. Recent experimental studies hypothesized that the ‘protein crowding’ effects are more dominant than the ‘protein-insertion’ effects, which we also plan to test using molecular simulations. Atomistic level details of protein-membrane interaction and protein induced membrane remodeling obtained from molecular simulations would guide the experimentalists to design controlled experiments to test various hypothesis required for understanding functions of the membrane proteins. Results of molecular simulations would be useful for designing drugs to inhibit membrane binding affinity of proteins and also to disable membrane bending activity of virus proteins that cause viral infection through membrane fusions. |
Total Budget (INR): | 20,46,000 |
Organizations involved