Agrawal, Ashutosh2022-06-19August 2022021-08August 202Portions of this document appear in: Joseph, J. G., Osorio, C., Yee, V., Agrawal, A., & Liu, A. P. (2020). Complimentary action of structured and unstructured domains of epsin supports clathrin-mediated endocytosis at high tension. Communications biology, 3(1), 1-16.https://hdl.handle.net/10657/9402Gaining mechanistic insights into membrane-protein interactions is vital for compre-hending cellular processes and health disorders. In this work, we pursued two sets ofstudies to elucidate such interactions. First, we used atomistic studies to investigate in-creased binding affinity of a membrane-remodeling protein (epsin) to membranes subjectedto high tension. We performed umbrella sampling calculations to provide the first quantita-tive evidence that tension energetically promotes the insertion of a transmembrane helicaldomain of epsin. Next, we embarked on an ambitious journey to build a coarse-grainedMonte Carlo computational framework to simulate membrane-protein interactions at themesoscale. This framework utilizes building blocks such as body, bonded and non-bondedcomponents and discretized differential geometry operators necessary to create interactionsof customizable molecules with a highly versatile membrane. We provide a concise overviewof the key notions underlying this framework. Next, we demonstrate the unique abilitiesof this framework via several toy problems inspired from biological systems. We simulated,to the best of our knowledge, the highest genus membrane structure in the literature tilldate. This structure resembles a nuclear envelope and consists of two adjacent sphericalmembranes fused at hundreds of sites. Next, we demonstrated the formation of coexistentdomains on an ellipsoidal vesicle generated by heterogeneous lipid composition. Next, wedemonstrated the assembly/disassembly of a tri-legged protein (called clathrin) on a vesi-cle and the ability of the polymerized protein to form cargo-carrying vesicles. Finally, weshow extreme tubulation caused by aggregation of banana-shaped proteins on a sphericalmembrane. These test cases confirm the potential of our new framework to model complexmembrane geometries and membrane-protein interactions.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).mebrane Monte Carlo2022-06-19Thesisborn digital