This document summarizes Vernon Dutch's computational analysis of chromatin utilizing interactive chromatin modeling. It discusses modeling chromatin structure using tools like ICM Web and LAMMPS molecular dynamics simulation. LAMMPS is used to minimize energy and prevent impossible steric collisions in the chromatin structure. Different potentials like Leonard-Jones are used to model interactions between DNA and nucleosomes. The results of phase I and II energy minimization are presented and compared. It concludes that this is a tool to explore, not predict, DNA structure and more experimentation is needed with multiple chromosomes.

1. Computational Analysis of Chromatin
Utilizing Interactive Chromatin Modeling
By Vernon Dutch
Advisor: Dr. Thomas Bishop

2. The Biology and Physics Behind it All
• What is Chromatin
• Reasons for modeling Chromatin

3. Brief History of DNA
• Watson and Crick
• Human Genome Project

4. Model of a Chromatin fiber

5. Inputting Data into ICM
• What is ICM Web
• Purpose of the ICM Web
• Inputting Data

6. Chromatin Folding and Energy of Nucleosome

7. Positioning
Problems of
Steric Collisions
• Impossible steric collisions
occur.
• No minimization applied

8. Utilizing LAMMPS
• LAMMPS is a classical molecular dynamics
simulation program
• Processes input files containing relevant atomic
data to produce the output data of molecule
behavior.

9. Utilizing LAMMPS
• These input scripts include the following
• Initialization—system of units, processors, force-field parameters
• atomic definitions---molecular biology or atoms on lattice
• settings----force field coefficient , simulation parameters, output option
• simulation commands----- initiate data processing

10. LAMMPS interaction with VMD
• Virtual Molecular Dynamics program (VMD) used to
view a three dimensional model of the chromatin.
• Examinable to ensure that proper behavior and energy
minimization occurs to prevent improbable steric collisions.

12. Comparison of atomistic and coarse grain approach

13. Minimization Process
• There are two possible cases of equations used for
minimization
• The simple soft-core that corrects possible worse case
scenarios with repulsion.
• More sophisticated nucleosome bead that is designed to
produce the needed geometry.
• Using the two phase method, we can make a system of
comparisons with multiple chromosomes data.

14. Energy Model
𝑈𝑠ℎ𝑜𝑟𝑡 𝑟𝑖𝑓 = { 4 ∈ (
𝜎
𝑟𝑖𝑗− 𝑝𝑖𝑗
)6 − (
𝜎
𝑟𝑖𝑗 − 𝑝𝑖𝑗
)12 + ∆
Korolev’s Lennard-Jones Potential
𝑟𝑒𝑓𝑓 𝑝𝑖 𝑝𝑖𝑗 𝑟𝑐𝑢𝑡
DNA-DNA 8.91 8 16 16 +
6
2𝜎
Octamer-Octamer 31.18 33 66 66 +
6
2𝜎
DNA-Octamer 20.05 20.5 41 41 +
6
2𝜎
𝜀 = 𝑘𝑇 = 0.593
𝑘𝑐𝑎𝑙
𝑚𝑜𝑙
, 𝜎 = 4Å , Δ = 0.25𝜀 shift
The cutoff of force and energy evaluation is chosen to coincide with
separation distance. This causes pairwise forces to be repulsive. This
removes steric overlap in ICM models.

15. Leonard-Jones Potential for LAMMPS
LAMMPS LJ/expand
Pair_coeff
ε σ ∆ 𝑟𝑐𝑢𝑡
DNA-DNA 0.593 4 16 4
6
2
Octamer-Octamer 0.593 4 66 4
6
2
DNA-Octamer 0.593 4 41 4
6
2
LAMMPS LJ/cut
Pair_coeff
ε σ 𝑟𝑐𝑢𝑡
DNA-DNA 0.593 18.25 16+ 4
6
2
66+ 4
6
2Octamer-Octamer 0.593 62.74
41+ 4
6
2DNA-Octamer 0.593 40.49
E= 4 ∈ (
𝜎
𝑟−Δ
)6 − (
𝜎
𝑟−Δ
)12
E= 4 ∈ (
𝜎 𝑙𝑗
𝑟
)6 − (
𝜎 𝑙𝑗
𝑟
)12

16. The PHASE I RESULT

17. The PHASE II RESULT

18. Conclusion
It is tool that explores, not predicts DNA.
Experiment with minimization calculations with more
chromosomes to fix “kinks”

19. THANK YOU !!!
Dr Bishop
Dr. Sawyer
Bishop Research Group---James Liman, Victoria Bamburg, Chitturi, Venkat, Pardhu
Louisiana Biomedical Research Network (LBRN)
Louisiana Alliance for Simulation-Guided Material Application (LA-SIGMA)
Of Course….. Louisiana Tech University

20. QUESTIONS???