1. Monte carlo simulations on mixed resolution protein models
Sundar Raman Subramanian
Zuckerman Lab
MMBioS meeting
5/29/2014

2. Quality of the Model vs Computational cost
Modeling of HIV protease at various resolution to sample the flap region
Dynamics of this flap influences the binding affinity of Ligand/Inhibitor to HIV protease
Quality of the Model
Computational Cost
Fully Atomistic
Mixed Resolution
Fully coarse grained

3. HIV Protease- Flap Dynamics
Starting structure
Flap in closed conformation
PDBID: 1HPX
without Ligand
Total amino acids per chain is 99
All atom Residues:
chain A: 45 to 54
Chain B 45 to 54
Coarse Grained Residues
chain A: 1 to 45
chain B: 55 to 90
90°

5. Mixed Resolution for Ligand Docking
Structure of Estrogen Receptor alpha with Estrogen
Coarse-grained region is shown in Pink
All atom region is Estrogen and receptor amino acids within 6Ang. of Estrogen
CG side chains has atomistic details and AA side chains interact with them atomistically
(PDBID: 1ERE)

7. Recovery of Estrogen Binding Pose
Collaborators: Prof. Andrew Stern & Prof. Steffi Oesterreich Labs

8. Ligand Spotlight: Ligand Decides the Resolution of Protein Residues
Interaction of ligand with Cyclin-dependent kinase 2

9. Challenges and Future Directions
Improvements on side chain interactions of coarse grained residues (better Go model?)
Optimization of parameters
Automated process for the preparation of ligand parameters
Tests on various systems
Heat shock proteins
Mutants of Estrogen receptor
Binding of ligands to Estrogen receptor and its mutants