Calculating the Potential of Mean Force with Replica Exchange Method in Explicitly Solvated Decalani

1
Calculating the Potential of Mean Force with
Replica Exchange Method in Explicitly Solvated
Decalanine SystemShenyu Kuang Department of
Chemistry and Biochemistry University of Notre
Dame
2
Contents

• Significance of Decalanine System
• Why calculate PMF?
• What is REM?
• How to get our job done?
• Current results and difficulties

3
Decalanine System

• Moderate Complicity
• Folding Activity
• Reference for
• Larger System
• Simulation Method

4
Potential of Mean Force (PMF)?

• Reaction coordinate
• End-to-end distance
• For the canonical ensemble
• Helmholtz free energy profile (i.e. PMF)

5
Replica Exchange Method (REM)?

• Parallel tempering brute force
• Metropolis criterion
• Simulation Environment
• NAMD
• Explicitly Solvated System only
• Fast
• ProtoMol
• Both Explicitly and Implicitly Solvated System
• Not so fast

6
Procedure
Unsolvated System
Solvating with VMD
Solvated System
Minimizing Equilibrating with NAMD
Equilibrated Solvated System
Simulating with REM by NAMD
Data Analysis
Final Simulated System
7
Solvating with VMD

• Rectangular water box
• X 2.9nm
• Y 4.6nm
• Z 2.9nm

8
Minimizing with NAMD

• Temperature 300K

9
Equilibrating with NAMD
10
Equilibrating with NAMD
11
REM simulation

• Simulation conditions (planned)
• 300 600 K
• 8 replicas
• Vacuum vs. solvated system
• Current difficulties
• Simulation jobs submitted NOT terminating
  properly
• Problem occurring even in very small running
  steps
• Possible reason code has infinite loop?

12
Further Work Needed

• Untangle the above problem and finish REM
  simulation
• Use simulation data to compute end-to-end
  distance data
• Use end-to-end distance data for histogram
• Use histogram to calculate PMF

13
Acknowledgement

• Prof. Izaguirre
• Dr. Trevor Cickovski
• Dr. Yuhui Lu
• Ms. Yao Shen

Thank You!