|2006 Summer Workshop San Diego, California
(click on figure for large version)
- Charles L Brooks III,
Department of Molecular Biology, The Scripps Research Institute
- Michael Feig,
Department of Biochemistry and Molecular Biology, Michigan State University
- Wonpil Im,
Department of Molecular Sciences, The University of Kansas
- Alex MacKerell,
School of Pharmacy, University of Maryland
- Lennart Nilsson,
Department of Biosciences at NOVUM, Karolinska Institute
- Jianhan Chen, The Scripps Research Institute
- Mike Crowley, The Scripps Research Institute
- Jana Khandogin, The Scripps Research Institute
- Workshop Reading
Monday, July 31
- 8:30 AM - 9:45 AM - Welcome, historical overview and introduction to
molecular mechanics and modeling with CHARMM and the MMTSB Tool Set. (Brooks)
- Welcome and overview of MMTSB and CTBP objectives
- Introduce CHARMM and the MMTSB Tool Set with an historical perspective
- A brief overview of methods in molecular modeling & nature of force field,
minimization and molecular dynamics, introduction to periodic boundary conditions
- A brief introduction to the flow of CHARMM calculations
- Comments on scope and range of problems that can be addressed with CHARMM,
e.g., from atomic detail, md, MC, MM, QM/MM, to multi-scale, simplified models
(Go-models, multi-resolution GNMs and minimalist protein/NA models).
- 9:45 AM - 11:00 AM - CHARMM force fields, parameterization strategies and
future/ongoing force field developments. (MacKerell)
- The nature of the CHARMM force field, molecular fragments and parameterization
- Current advances in fixed charge force fields
- Extending fixed charge force fields for "new molecules"
- Polarizable force fields - ChEq, PIPF and Drude models
- 11:00 AM - 12:00 PM - Introduction to MMTSB scope and functionality. (Feig)
- Overview of MMTSB scope, purpose and structure
- Description of tools their function and extensibility
- Introductory examples/illustrations
- 2:00 PM - 5:00 PM - Elementary applications to peptides, proteins and nucleic acids
(Brooks, MacKerell, Feig).
- Visualizing molecules and trajectories with VMD
- Building, minimizing and solvating an α-helical peptide
- C-peptide from RNAse A.
- Conditioning/preparing a multi-domain protein for simulation
- with CHARMM all atom force field
- using MMTSB Tools convpdb.pl, minCHARMM.pl, enerCHARMM.pl
- with CHARMM polarizable ChEq force field
- Conditioning/preparing DNA for molecular dynamics
- with CHARMM DNA/RNA force fields
- using MMTSB Tools
- Application of MM-GBSA to protein-protein and protein-DNA complexes
- Calculating protein-small molecule (fragment/drug) interactions with CHARMM
- Setting-up and running molecular simulations with CHARMM through the MMTSB Tool Set
- Ensemble and ensemble calculations through the MMTSB Tool Set
- MMPB/SA type analysis
- analysis example w/ clustering
Tuesday, August 1
- 8:30 AM - 9:30 AM - CHARMM analysis tools and facilities. (Nilsson) (download lecture)
- Overview of CHARMM analysis facilities and trajectory analysis
- Illustrative examples of solvent analysis, hydrogen bonding, clustering w/
K-means cluster facility
- 9:30 AM - 10:45 AM - Simulating membranes and protein-membrane systems. (Im) (download lecture)
- Membrane force fields and system set-ups in CHARMM
- Key properties and observables
- Illustrative example (KcsA or gA)
- 11:00 AM - 12:00 PM - Implicit solvent models. (Im) (download lecture)
- Overview of CHARMM empirical implicit solvent models (ASA, EFF,IMFF)
- Continuum solvent models in CHARMM (PB, GB)
- Continuum-based boundary models
- Introductory examples/illustrations – folding, membrane simulations, etc.
- 2:00 PM - 5:00 PM - Applications to membrane/protein systems, implicit solvent
simulations and trajectory analysis. (ln, wi, mf)
- Comparative analysis of protein structures (e.g., rmsd versus reference,
hydrogen bonding, secondary structure
- Examples of analysis of solvent/solvation structure and dynamics
- Clustering molecular trajectories based on backbone conformations
- Clustering molecular trajectories based on properties using MMTSB Tools (w/ Feig)
- Analysis of NMR properties, order parameters, T2, etc.
- Conditioning/preparing membrane systems for molecular dynamics
- Sampling ion conformations for conductivity calculations
- Poisson Boltzmann calculations in CHARMM - mapping the electrostatic potential from
- Preparing and setting-up a protein system for molecular simulations with CHARMM
- Membrane GBSW simulation of phospholamban
Wednesday, August 2
- 8:30 AM - 9:30 AM - Free energy calculations, umbrella sampling and pmfs. (Nilsson) (download lectures part 1 and part 2)
- Introduction and overview to CHARMM free energy methods and restraints
- Illustrative examples from base flipping
- 9:45 AM - 11:00 AM - Using the MMTSB Tool Set with MONSSTER and CHARMM for
protein structure prediction (Feig) (download lecture)
- Overview of structure prediction capabilities
- Applications from homology/loop modeling to de novo structure prediction
- 11:00 AM - 12:00 PM - Replica-exchange molecular simulations with CHARMM and MMTSB (Im) (download lecture)
- Theoretical background of replica exchange MD
- illustrative examples for membrane assembly, peptide folding and protein refinement
(w/ Jianhan Chen)
- 2:00 PM - 5:00 PM - Structure prediction, free energy calculations and replica-exchange
- Analysis of free energy changes from molecular simulations
- Structure prediction set-up and analysis
- REX-MD for membrane peptide folding
- Refinement of NMR and/or homology models with REX-MD and GB
- Setting-up and running molecular simulations with CHARMM membrane GBMV on phospholamban
- Multiple dielectric simulations with GBMV
- New analysis tools in MMTSB - examples
- 5:30 PM - 7:00 PM - Workshop barbecue at Natural Science Building Patio
- 7:00 PM - 9:00 PM - Participant poster session and social at Natural Science Building Atrium
- Poster set-up to begin at 7:00 PM, munches and drinks to be supplied
Thursday, August 3
- 8:30 AM - 9:30 AM - Developing and implementing multi-resolution models with CHARMM. (Brooks) (download lecture)
- Topological and flavored Go models for the investigation of protein folding and unfolding.
- Multi-scale DNA models for DNA structure and thermodynamics
- 10:00 AM - 11:00 AM - Integrating multi-scale, multi-resolution models with detailed atomic
models to explore reaction pathways in DNA polymerases (Arora)
- 11:00 AM - 12:00 PM - Multi-scale modeling, multi-scale ion channel simulation using BD and
PNP (Im) (download lecture)
- 2:00 PM - 5:00 PM - Multi-scale, multi-resolution modeling
- Using CHARMM and MMTSB to explore protein folding mechanism and thermodynamics
- Exploring single molecule protein pulling experiments with Go models
- Thermodynamic analysis of DNA melting with CHARMM MC and multi-scale DNA model
- Constructing and refining a conformational transition pathway using Gaussian
networks with CHARMM
- Structure prediction set-up and analysis
Friday, August 4
- 8:30 AM - 9:15 AM - Research Seminar, L. Nilsson - Ligand interactions with nuclear hormone receptors.
- 9:15 AM - 10:00 AM - Research Seminar, M. Feig - Protein structure prediction and refinement.
- 10:00 AM - 10:45 AM - Research Seminar, A. Mackerell - Base flipping in the presence of the
cytosine-5-methyltransferase from HhaI.
- 10:45 AM - 11:30 PM - Research Seminar, W. Im - Where are we after one year?
- 11:30 AM - 12:00 PM - Brooks - Summary and final comments.
- 2:00 PM - 5:00 PM - Final hands-on, finish up tutorial materials, one-on-one interactions
(Brooks, Feig, Im, MacKerell, Nilsson, Khandogin, Chen, Crowley)
- Moonlight Kayaking on Mission Bay
- 6:00 PM - 10:30 PM
We have organized a moonlight kayaking trip for the workshop participants on the evening of Friday,
August 4. We have planned a BBQ dinner at the Mission Bay Aquatic Center from 6:30 - 7:30 followed
by three hours of kayaking on Mission Bay during which time Sea World may be having a fireworks display.
A bus will be departing from UCSD at 6:00 PM and returning about 10:30 PM.
The trip will be limited to 30 participants so if you would like to go, please let us know no later
than Wednesday, July 26.
There will be a cost of $40 for this activity. Payment can be in cash or via a check made out to "UC Reagents"
on the first day of the workshop. If you have any questions, please contact
- Workshop ends
We acknowledge Apple Computer for providing machines and assistance in making the workshop a success.