Difference between revisions of "Team:Queens Canada/Model"

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Revision as of 01:59, 11 October 2018

At team Queens Canada, we believe that proper preparation is the best way to reach a desired outcome. Accordingly, we sought to model many aspects of our project which aided in making the right choices in the lab and receiving positive results. Through the help of student on our team specializing in biomedical computing, applied mathematics, and chemical engineering, we created a number of different models that were crucial to our project design.

Molecular Dynamic Simulations

One of our constructs relied on linkers of sufficient length and flexibility to convert a conformational change, into signal transduction. We have achieved this through firstly modeling with PyMol [[[[LINK TO LINKER DEVELOPMENT TAB]]] and then performing molecular dynamic simulations of the root-mean-square deviation of atomic position [[[LINK TO Molecular Dynamics Tab]]]].

RMSD0

Introduction

Michaelis - Menten kinetics is a model used to examine enzyme kinetic. Luciferase's activity can be modeled by Michaelis-Menten kinetics as they perform the simple conversion of a substrate into a product and a photon. Our project relied on the light producing NanoLuc Luciferase as a signal in our devices. We were able to model this relationship with MATLAB. The governing equations for this model were compiled in the MATLAB, with the goal of creating a generic calculator which teams may use in the future. Known values for concentrations and reactions rates are used as inputs, and the file produces the various rates of change with respect to the concentrations.

RMSD0

An example Michaelis-Menten graph demonstrating the relationship between substrate concentration and enzyme activity

Computer Aided Design

Pacifier Design - Nipple, Cherry Baglet Vs. One way flow. Negative Pressure


Modeling

We determined that the linkers between the GR-LBD and the inteins halfs would need to be flexible as there is no direct path connecting the termini and they would require the flexibility to meet each other and produces a trans-splicing event. To determine which linker would be ideal we ran simulations of Root-mean-square deviation of atomic positions to determine optimal linker length and composition. Firstly we chose various linker designs inspired from previous work [a,b], then the entropy equations were run on the Queen’s University Computer Cluster for 7 days by Dr. Campbell.

  1. http://parts.igem.org/Protein_domains/Linker
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726540/

Another aspect of our project we south to model, was which pacifier design would allow for optimal detection of the luminescence signal. Eric modelled this through a MatLab simulation of the “Narrow escape problem”....