Beruflich Dokumente
Kultur Dokumente
pdf
updated on May 13, 2012
Wonpil Im
Department of Molecular Biosciences and
Center for Bioinformatics
University of Kansas
http://im.bioinformatics.ku.edu
http://www.charmm-gui.org
http://www.glycanstructure.org
Ion Channels
KcsA K+ channel
rhodopsin
Ion Channels
KcsAclass
K+ channel
The largest
of drug target
rhodopsin
Golgi Apparatus!
Endoplasmic !
Reticulum!
Nucleus!
Mitochondria!
http://www.usd.edu/~bgoodman/ReviewFrames.htm!
Amusing, but
Golebiewska, Kay, Masters, Grinstein, Im, Pastor, Scarlata, McLaughlin (2011) Mol. Biol. Cell 22:3498-3507
Hi guys,"
"
This little movie might amuse you. Rich and Wonpil: "
Dictyostelium is a slime mold or social amoeba. It lives alone when the living is easy, "
but when it gets cold and dark, it huddles together, forming slugs and fruiting bodies. "
In this example, a lone guy is trying to eat "
a yeast that is just too long."
"
"
PIP2 in green, actin in red."
"
"
Cheers"
Stuart"
Ion Channels
KcsA K+ channel
rhodopsin
Membrane Protein:
Parameter Files:!!
!top_all22_prot.rtf!
!par_all22_prot.prm!
!top_all27_na.rtf!
!par_all27_na.prm!
!top_all36_carb.rtf!
!par_all36_carb.prm!
!top_all36_lipid.rtf!
!par_all36_lipid.prm!
!top_all36_cgenff.rtf!
!par_all36_cgenff.prm!
from CHARMM-GUI!
!toppar_water_ions.str!
!toppar_all36_lipid_cholesterol.str!
!toppar_all36_glycopeptide.str!
!toppar_all22_prot_fluoro_alkanes.str!
!toppar_all22_prot_aliphatic_c27.str!
- toppar.str!
reading all top & par files!
- toppar directory!
L=S
C1
1
2
lipid tails
(hydrophobic)
Fatty acids:
saturated
monounsaturated with one double bond
polyunsaturated with multiple double bonds
POPC
1-palmitoyl2-oleoyl
phosphatidylcholine
SAPC
1-stearoyl2-arachidonoyl
phosphatidylcholine
Klauda, Venable, Freites, OConnor, Tobias, Mondragon-Ramires, Vorobyov, MacKerell and Pastor (2010) J. Phys. Chem. B 114, 78307843
SCD
1
= 3cos2 ! CH !1
2
CHARMM-GUI!
Membrane Builder!
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
step3_packing.pdb!
+ image atoms!
Please have a look at it!!
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Lipid Generation!
[step4.1_lipid.inp]!
Protein/Bilayer
ASSEMBLY
Protein/Bilayer
Protein/Bilayer
Protein/Bilayer
Different Membranes
Monolayers
Micelles
Vesicles
PIP2
cardiolipin
lipopolysaccharide
Lipopolysaccharide Membranes
10 25 repeating units
each unit with 3-6 linear or branched sugars
highly variable
Lipopolysaccharide Membranes
Jo, Wu, Stuhlsatz, Klauda, MacKerell, Widmalm, and Im (2012)
Methods in Molecular Biology: Glycoinformatics (submitted)
Membrane Analyzer
Have you ever imagined a web-based toolset for !
membrane simulation trajectory analysis?!
Updates on CHARMM-GUI
Solvator"
Quick MD Simulator"
Targeted/Steered/Pulling "
MD Simulator"
Membrane Builder"
Path Finder"
QM/MM Simulator"
PBEQ Solver"
REX-MD Simulator"
EMAP Utilizer"
Glycan Reader"
Ligand Reader"
available now"
work in progress"
future plan "
PBEQ Solver
Jo, Vargyas,Vasko-Szedlar, Roux, and Im (2008) Nucl. Acids Res. 36:W270
Online Visualization!
Glycan Simulation
Basic structure of
carbohydrate
Carbohydrate can
be linear / cyclic
lactose
amylose
Why Glycan?
Gal
GlcNAc
Neu5Ac
Man
Fuc
Why Glycan?
1. Glycans modulate protein structure, dynamics, and function
2. Glycans are related to vaccine developments
3. There are critical needs for a general tool for glycan modeling and simulation
anti-inflammatory
pro-inflammatory
16
14
16
12
13
14
14
14
12
Gal
GlcNAc
Neu5Ac
Man
Fuc
Why Glycan?
1. Glycans modulate protein structure, dynamics, and function
2. Glycans are related to vaccine developments
3. There are critical needs for a general tool for glycan modeling and simulation
HIV gp120 envelop protein has lots of glycans, about 50% of the total mass
Trimeric spike
Why Glycan?
1. Glycans modulate protein structure, dynamics, and function
2. Glycans are related to vaccine developments
3. There are critical needs for a general tool for glycan modeling and simulation
Why Glycan?
1. Glycans modulate protein structure, dynamics, and function
2. Glycans are related to vaccine developments
3. There are critical needs for a general tool for glycan modeling and simulation
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
cyclodextrin
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
Glycan Reader
Jo, Song, Desaire, MacKerell, and Im (2011) J. Comput. Chem. 32:3135-3141
+
Find right orientation
Close contact
Rearrangement
Binding
Desolvation
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
Step1:
PDB Reading
Step 2:
Solvation
Step 3:
Boundary
Potential
Step 4:
Equilibration
Site
Step 5:
Free Energy
Simulation
GSBP
Step 3:
Boundary
Pontential
Step 2:
Solvation
Bulk
Step 6:
WHAM
Buffer
Implicit
SSBP
Benzene
T4 Lysozyme
PDB: 181L
Implicit
Explicit
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
Step1:
PDB Reading
STEP1
Input
Output
STEP2
Input
Output
STEP3
Input
Output
Step 2:
Solvation
Step 3:
Boundary
Potential
Step 4:
Equilibration
Step 5:
Free Energy
Simulation
Filename
step1_pdbreader.inp
Description
Input files for structure initialization
step1_pdbreader.pdb
@lig/@lig.rtf
@lig/@lig_g.rtf
@lig/@lig.prm
@lig/ndihe.stsr
step2.1_site_solvator.inp
step2.2_bulk_solvator.inp
step2.1_site_solvator.pdb
step2.2_bulk_solvator.pdb
step3.1_gsbp_setup.inp
step3.2_ssbp_setup.inp
config.py
step3_job.pbs
step3.1_gsbp_setup.pdb
step3.1_gsbp_setup.mij
step3.1_gsbp_setup.phix
step3.2_ssbp_setup.pdb
Step 6:
WHAM
Ligand Binder
Jo, Jiang, Lee, Roux, and Im (2012) submitted
STEP4
Input
Output
STEP5
Input
STEP6
Input
Filename
step4.1_site_gcmc.inp
step4.2_site_equil.inp
step4.3_restraint_setup.inp
step4.3_restraint_geo.str
step4.3_restraint_geotest.str
step4.3_restraint_ref.str
step4.4_bulk_equil.inp
step4_job.pbs
step4.1_site_gcmc.crd
step4.2_site_equil.dcd
step4.2_site_equil.crd
step4.3_restraint_geo.prm
step4.3_restraint_geo.pdb
step4.3_restraint_ref.prm
step4.3_restraint_consdihe.str
step4.3_restraint_ligave.pdb
step4.4_bulk_equil.pdb
step5.1_site_fes.inp
step5.1_site_gconst.str
step5.2_bulk_fes.inp
step5_jobmanager.com
step5_template.pbs
Description
Adjust the number of water molecules in GSBP
Equilibration of SITE system
Setup anchoring atoms and restraint parameters
Determine anchoring atoms
Test validity of anchoring atoms
Determine the restraint parameters
Equilibration of BULK system
Example PBS script for batch system
SITE system after adjustment of number of water
Trajectory of equilibration of SITE system
Last snapshot of equilibrated SITE system
Anchoring atom definition
Anchoring atoms (named as DUM)
Reference values for restraint potential
Symmetric group restraints
Average structure of bound ligand during equilibration
Last snapshot of equilibrated BULK system
FEP/MD input for SITE system (including PMF input)
Restraints setup for orientation/translation restriction
FEP/MD input for BULK system (including PMF input)
Script for submitting batch jobs
Example PBS script for batch system
step6.1_wham_fep.inp
step6.1_wham_fep.pbs
step6.2_wham_rmsd.inp
step6.2_wham_rmsd.pbs
step6_wham.com
step6_table.py
GCMC/BD simulation
Total time 1.5 ns
15 ps/frame
150 mV
1 M [KCl]
K+
Cl-
Buffer 1
Itot
IK
ICl
asymmetric
solutions
PG-1 Oligomer
VDAC
-Hemolysine
Anthrax PA-pore
Acknowledgment
Group Members
Collaborators
postdoc
graduate
undergraduate
Huan Rui
Kevin C. Song
Sunhwan Jo
Danielle Stuhlsatz
Xi Cheng
John Kim
Dr. Emilia Wu
Andrew Beaven
Phillip Morris
Jacob Wilson
Vidyashankar Iyer