viii
Abstract
Molecular Simulations of Monomeric sarcosine oxidase
Shyno Mathew
Advisor: Prof. Cameron F. Abrams
Monomeric sarcosine oxidase (MSOX) is a flavoenzyme that catalyzes the oxidation of
sarcosine to form formaldehyde, glycine and hydrogen peroxide. MSOX also reduces
molecular oxygen. There is no channel detected by experiment that transports oxygen
from the protein surface to the buried active site for oxygen reduction. The main purpose
of this work is to determine the oxygen transport channels in MSOX using molecular
simulations. Here we used two methods: Molecular Dynamics (MD) and Single-sweep
free energy reconstruction. Our results show that there exist two different pathways to the
oxygen activation site: the so called si-side and re-side entry pathways. Between these
two, the si-side entry pathway is more thermodynamically favorable. This highlights the
efficiency of MSOX because the substrate and O2 access the catalytic center via two
distinct pathways.