Using Molecular Dynamics to Examine the Effect of a Novel L505H Mutation on Drug-Resistant B-Raf-V600E and to Understanding the Mechanistic Role of the Mobile Loop Region in Alkanesulfonate Monooxygenase

Abstract

Two main projects were studied in this work: 1) the effect of type I and type II inhibitors on B-Raf V600E and the B-Raf V600E-L505H mutations 2) the mechanistic role of the mobile loop in SsuD in alkanesulfonate monooxygenase. Chapter 1 describes the background of the two different systems studied. Chapter 2 describes the theory of the computational methodology used in these studies. Chapter 3 reports the results of the simulation carried out on B-Raf V600E and B-Raf V600E-L505H in order to show the differences in inhibitor binding. Chapter 4 shows the computational results pertaining to the mobility of the dynamic loop for the SsuD component of alkanesulfonate monooxygenase and its role in catalytic activity.