MMTSB/CTBP Summer Workshop
July 31 - August 4, 2006

Molecular simulation and structure prediction using CHARMM and the MMTSB Tool Set
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
Access to the workshop tutorial pages.
Useful Links
Lectures: 8:30 AM - 12:00 PM at Asante classroom A+D
Hands-on: 2:00 PM - 5:00 PM at Natural Science Building 1205
Schedule: Monday, Tuesday, Wednesday, Thursday, Friday
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) (download lecture)
  • 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) (download lecture)
  • The nature of the CHARMM force field, molecular fragments and parameterization strategies
  • 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) (download lecture)
  • 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,,
    • 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 protein mutations
  • Preparing and setting-up a protein system for molecular simulations with CHARMM GBSW/GBMV approaches
  • 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.