MMTSB/CTBP Summer Workshop
August 4-7, 2009

Molecular simulation and structure prediction using Amber, CHARMM, and the MMTSB Tool Set
2009 Summer Workshop San Diego, California
Instructors
  • Charles L Brooks III, Department of Chemistry, University of Michigan
  • Michael Feig, Department of Biochemistry and Molecular Biology, Michigan State University
  • David A. Case, Biomaps Institute, Rutgers University
  • Ross C. Walker, San Diego Supercomputer Center, University of California San Diego
  • Jana Shen, Department of Chemistry, University of Oklahoma
  • Jianhan Chen, Department of Biochemistry, Kansas State University
Mentors
  • Jennifer Knight, Department of Chemistry, University of Michigan
  • Sishi Tang, Biomaps Institute, Rutgers University

Workshop Reading
Tutorials
Access to the workshop tutorial pages.
Useful Links
Agenda
Lectures: 8:30 AM - 12:00 PM Humanities & Social Sciences (HSS) Building 1330
Hands-on: 2:00 PM - 5:00 PM Natural Sciences Building (NSB) 1205
Schedule: Tuesday, Wednesday, Thursday, Friday
Tuesday, August 4
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, AMBER 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.
  • The nature of the CHARMM force field, molecular fragments and parameterization strategies.

9:45 AM - 10:00 AM - Coffee Break

10:00 AM - 11:00 AM - The AMBER program suite for simulations of molecular systems (Case) (download lecture)
  • Introduce AMBER with an historical perspective.
  • A brief introduction to the flow of AMBER calculations.
  • Comments on the scope and range of problems that can be addressed with AMBER.
  • The nature of the AMBER force field, molecular fragments and parameterization strategies.

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

12:00 PM - 2:00 PM Lunch

2:00 PM - 5:00 PM - Elementary applications to peptides, proteins and nucleic acids (Brooks, Case, Walker, Feig and mentors).


Brooks/Feig

Case/Walker
  • Preparing DNA and RNA for molecular dynamics (Tutorial).
    • with AMBER DNA/RNA force fields
    • using MMTSB Toolset
    • Use of W3DNA ( http://w3dna.rutgers.edu/) to build DNA starting structures.

7:00 PM - 10:00 PM Participant poster session with drinks and munchies.

Wednesday, August 5
8:30 AM - 9:30 AM - CHARMM analysis tools and facilities. (Chen) (download lecture)
  • Overview of CHARMM analysis facilities, trajectory analysis, NMR module.
  • Illustrative examples of solvent analysis, hydrogen bonding, clustering w/ K-means cluster facility

9:30 AM - 9:45 AM CoffeeBreak

9:45 AM - 11:00 AM - Implicit solvent models in CHARMM and Amber. (Chen/Case) - Chen: (download lectures)
  • Overview of CHARMM empirical implicit solvent models (ASA,EFF,IMFF)
  • Continuum solvent models in CHARMM (PB,GB)
  • Overview of AMBER GB implicit solvent models

11:00 AM - 12:00 PM - Introduction to AMBER's Antechamber and the General AMBER Force Field (Tang) (download lecture)
  • Overview of General AMBER Force Field. Antechamber, automated atom type and parameter selection for ligands.
  • Examples of combining GAFF with protein force fields (FF99SB).
  • Problematic systems to be aware of.

12:00 PM - 2:00 PM Lunch

2:00 PM - 5:00 PM - Applications to membrane/protein systems, implicit solvent simulations and trajectory analysis. Use of AMBER's Antechamber module. (Chen, Feig, Case, Walker, Mentors)
Chen/Feig
  • Basic analysis of MD trajectories with MMTSB Tool Set (MMTSB Introduction)
  • Advanced trajectory analysis with CHARMM (CHARMM Trajectory analysis)
    • 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
    • Analysis of NMR properties, order parameters, T2, etc.
  • Ensemble analysis and clustering with MMTSB Tool Set (Ensemble analysis)

Case/Tang/Walker
Feig

Thursday, August 6
8:30 AM - 9:30 AM - Replica-exchange molecular simulations with CHARMM and MMTSB (Chen) (download lecture)
  • Theoretical background of replica exchange MD
  • Illustrative examples for membrane assembly, peptide folding and protein refinement
  • Using umbrella sampling, WHAM analysis (w/Feig)

9:30 AM - 9:45 AM CoffeeBreak

9:45 AM - 10:45 AM - Constant pH molecular dynamics with CPHMD (Shen) (download lecture)

10:45 AM - 11:45 PM - QM/MM Simulations in Amber (Walker) (download lecture)

11:45 PM - 2:00 PM Lunch

2:00 PM - 5:00 PM - Replica exchange, constant pH and QM/MM (Shen, Feig, Chen, Walker, Mentors)


Chen/Feig

Shen
Walker
Friday, August 7
8:30 AM - 9:30 AM - Using the MMTSB Tool Set with Modeller and CHARMM for protein structure prediction (Feig) (download lecture)
  • Overview of structure prediction capabilities
  • Applications from homology/loop modeling to de novo structure prediction

9:30 AM - 9:45 AM CoffeeBreak

9:45 AM - 10:45 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

10:45 AM - 11:45 AM - Free energy simulations in Amber (Case) (download lecture)

11:45 AM - 2:00 PM Lunch

2:00 PM - 5:00 PM - Structure prediction, multi-scale, multi-resolution modeling, free energy (Brooks, Case, Feig)


Feig
  • Template-based structure prediction (Template predictions)
    • Secondary structure prediction through psipred
    • Sequence alignment through PSI-BLAST
    • Homology modeling through the MMTSB Tool Set
  • Loop modeling with Modeller and MMTSB Tool Set (Loop modeling)

Brooks
  • Using CHARMM and MMTSB to explore protein folding mechanism and thermodynamics
  • Exploring single molecule protein pulling experiments with Go models (Force protein unfolding)

Workshop ends
The workshop organizers wish to acknowledge the support of the National Science Foundation Physics Frontiers Centers program and the National Institutes of Health National Center for Research Resources program.