Sangho Ji. (2025). Molecular Mechanism of CB1 and G-protein using MD simulation and Coevolution approach. doi: 10.22677/THESIS.200000841438
Type
Thesis
Description
CB1, GPCR, MD simulation
Table Of Contents
Ⅰ. General introduction 1 1.1 G-protein coupled receptor (GPCR) 1 1.2 Cannabinoid receptor type 1 (CB1) 1 1.3 Molecular dynamics simulation 2 1.4 Aim of the research 3
PART Ⅰ. Understanding the role of the CB1 toggle switch in interaction networks using molecular dynamics simulation 5
Ⅰ. Introduction 5 1.1 Introduction: Toggle switch 5 Ⅱ. Method 8 2.1 Molecular dynamics simulation 8 2.1.1 Preparation of ligand-bound CB1 complex structure 8 2.1.2 System building and toggle switch mutation 8 2.1.3 Molecular dynamics simulation 8 2.2 Analysis of the MD simulation trajectory 9 2.2.1 CB1 substructure analysis 9 2.2.2 Calculating energy network 12 2.2.3 Visualization 12 Ⅲ. Results 13 3.1 Toggle switch-dependent molecular dynamics of the CB1 13 3.2 The change of helical orientations by toggle switch mutation 17 3.3 Analysis of interaction among CB1 helices and loops 22 3.4 The residual interaction network around Na+ pocket and extracellular loop 24 Ⅳ. Discussion 31 4.1 Discussion 31
PART Ⅱ. Elucidation molecular mechanism of activation CB1-G protein complex using MD simulation and Coevolution approach 37
Ⅰ. Introduction 37 1.1 Introduction: CB1-G protein 37 1.2 Statistical coupling analysis (SCA) 38 Ⅱ. Method 39 2.1 Molecular dynamics simulation 39 2.1.1 CB1-G protein complex structure preparation 39 2.1.2 Hetero molecule and Membrane system building 39 2.1.3 Molecular dynamics simulation 40 2.2 Analysis of the MD simulation trajectory 41 2.2.1 CB1-Gprotein structure analysis 41 2.2.2 Calculating energy network 44 2.2.3 Visualization 44 2.3 Statistical Coevolution Analysis 44 Ⅲ. Results 46 3.1 Structural dynamics of closed and open CB1-G protein complex 46 3.2 Difference residual interaction within CB1-G protein complex 50 3.2.1 Different interaction network of CB1 between closed and open complex 50 3.2.2 Different interaction network of closed and open Gα protein 55 3.3 Dynamic interaction change around GDP region in closed Gα protein 60 3.4 Identifying functional domains of Gα protein by SCA approach 64 Ⅳ. Discussion 70 4.1 Discussion 70
