CAN RANDOM PROCESSES CREATE ROBUST BEHAVIOUR IN CLATHRIN-MEDIATED ENDOCYTOSIS? AN IN-SILICO STUDY OF THE SELFASSEMBLY OF CLATHRIN AND PUTATIVE ROLES FOR THE DISORDERED REGIONS OF EPSIN AND EPS15.

Abstract

Stochasticity is an intrinsic feature of many natural processes. In this thesis, we study two processes in Clathrin-Mediated Endocytosis to see if stochastic processes at one scale might result in deterministic outcomes at a higher scale. The two processes are - the self-assembly of the coat protein Clathrin into cages, and the binding of the protein AP2 to long disordered regions in proteins Epsin and Eps15. To study Clathrin self-assembly, we design a Monte-Carlo simulating engine - CLASS (CLathrin ASsembly Simulator). We use this simulator to study how geometry and configuration-dependent binding affinities between Clathrin molecules might affect the morphologies of the lattices they form. To study Epsin/Eps15 we generate ensembles of structures of the disordered regions and study how the dimensions and energies of the structures vary when bound to multiple copies of a binding partner (AP2a). We speculate that the disorder of these regions, coupled to multiple AP2 binding sites, might be the basis for a deterministic role for these proteins in CME.