Difference between revisions of "2012 Workshop on Free Energy Methods in Drug Design"

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   Vijay Pande, moderator
 
   Vijay Pande, moderator
 
     7:45-8:30: Coffee and pastries
 
     7:45-8:30: Coffee and pastries
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     8:30-9: [ 25 min ] - ""
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     8:30-9: Charles L. Brooks, III [ 25 min ] - TBA
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     9-9:30: [ 25 min ] -  
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     9-9:30: David A. Case [ 25 min ] - "Using free energy to update force fields"
 
     9:30-9:50: Coffee break [ 20 min ]
 
     9:30-9:50: Coffee break [ 20 min ]
−
     9:50-10:20: [ 25 min ] - ""
+
     9:50-10:20: Daniel Zuckerman [ 25 min ] - "Simultaneous determination of equilibrium and non-equilibrium properties from the weighted ensemble (WE) method"
−
     10:20-10:50: [ 25 min ] - ""
+
     10:20-10:50: Michael Schnieders [ 25 min ] - "Accelerating polarizable multipole AMOEBA free energy calculations using orthogonal space methods"
 
     10:50-11:10: Coffee break [ 20 min ]
 
     10:50-11:10: Coffee break [ 20 min ]
−
     11:10-11:40:  [ 25 min ] - ""
+
     11:10-11:40:  Emilio Gallicchio [ 25 min ] - "Binding pathways, conformational sampling, and convergence: the shortest route is often not the fastest"
 
     11:50-12: Vijay Pande - moderated discussion
 
     11:50-12: Vijay Pande - moderated discussion
  
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   "You mean, we can use free energies for other things, too? Bound waters, permeation, and solubilities"
 
   "You mean, we can use free energies for other things, too? Bound waters, permeation, and solubilities"
 
   Kim Branson, moderator
 
   Kim Branson, moderator
−
     1-1:30: [ 25 min ] - ""
+
     1-1:30: Jonathan Essex [ 25 min ] - "Free energy calculations of the role of bound water in protein-ligand association"
−
     1:30-2: [ 25 min ] - ""
+
     1:30-2: Guanglei Cui [ 25 min ] - "SPAM: a simple approach of profiling bound water molecules and its application in lead optimization"
 
     2-2:20: Coffee break [ 20 min ]
 
     2-2:20: Coffee break [ 20 min ]
−
     2:20-2:50: [ 25 min ] - ""
+
     2:20-2:50: Jean-Francois Truchon [ 25 min ] - "What can we learn from integral equation theory: Using 3D-RISM free energies in modeling"
−
     2:50-3:20:   [ 25 min ] - ""
+
     2:50-3:20: Rommie Amaro [ 25 min ] - "Small molecule membrane permeability"
 
     3:20-3:40: Coffee break [ 20 min ]
 
     3:20-3:40: Coffee break [ 20 min ]
−
     3:40-4:10:   [ 25 min ] - ""
+
     3:40-4:10: Andrew Paluch [ 25 min ] - "Solubility prediction using free energy calculations and thermodynamic modeling"
 
     4:10-4:30: Kim Branson - moderated discussion
 
     4:10-4:30: Kim Branson - moderated discussion
 
     4:30-4:50: Short talk 1 (TBA) [ 15 min ]
 
     4:30-4:50: Short talk 1 (TBA) [ 15 min ]
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'''Poster session, mixer, and food -- Vertex lobby'''
 
'''Poster session, mixer, and food -- Vertex lobby'''
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=== Wednesday, May 23===
 
=== Wednesday, May 23===

Revision as of 20:42, 13 April 2012

2012 Workshop on Free Energy Methods in Drug Design

May 21-23, Cambridge, Massachusetts, USA

Aims

This workshop focuses on free energy techniques -- the latest innovations and use cases, force field parameterization as it touches these techniques, and sampling practices, among other things. We, the organizers, believe that these techniques are on the verge of being able to make an impact in appropriate drug discovery applications, but a number of challenges remain. This workshop provides a unique opportunity to assess where we are today and what challenges must be tackled next to bring the potential of free energy techniques to bear on real-world applications. We also seek to identify particular problems in drug discovery where these methods can have an impact.

Our goal in this workshop is to bring together experts from pharma and supporting industries, as well as academia, in an intense and focused workshop to identify challenges and help chart the path forward. We are particularly interested in hearing about use cases, pitfalls and their solutions, and so on. We also firmly believe we can learn a great deal from failure, so we hope participants will go beyond just highlighting success stories to provide more detailed insight into successes and failures.

We hope to draw talks on several main themes, including (1) use cases for free energy techniques in real-world problems where they can or have had an impact; (2) how pharma can benefit today or in the immediate future; (3) parameterization and how the latest innovations here affect free energies; and (4) good sampling practices and challenges facing sampling and their impact on free energy estimates. Talks should be focused on addressing these or related aims. As in our previous workshop, participants should feel free to discuss work that highlights problems or limitations, present ideas on how these limitations may be overcome, and discuss new developments that are underway.

Schedule Overview

  • Full days Monday, Tuesday, and Wednesday (contact D. Mobley if you are a presenter and will not be present for the whole meeting)
  • Conference dinner Monday night covered or subsidized by our sponsors (note change of night) at Firebrand Saints
  • Poster session/mixer with food and drinks in the Vertex lobby on Tuesday night (note change of night)

Organizers

  • Kim Branson, Discovery Engine email
  • John Chodera, University of California, Berkeley email
  • Richard Dixon, Vertex Pharmaceuticals email
  • David Mobley, University of New Orleans email
  • Vijay Pande, Stanford University email
  • Michael Shirts, University of Virginia email

Talks

In keeping with the (popular) format of our previous workshop, typical talks will be 25 minutes in length plus a few minutes for questions.

While this is a short format, it is in keeping with the goals of the workshop: We're after focused talks which highlight a particularly informative study or aspect in the area, not an overview of everything you've done in the field. We So, decide what to cover and stick to that material. Example topics might include:

  • An unresolved puzzle relating to a free energy study in some particular system
  • Sampling challenges facing application of free energy methods to a particular system, and ideas how to tackle these
  • A new sampling method and how it has been applied to resolve sampling problems in free energy calculations
  • Why free energy calculations for target X reliably crash and burn, but target Y seems much more tractable

Many others are possible. The point is, we're not after a sales pitch for free energy methods -- we want to hear what you find works, what doesn't work, and what you know or think about why.

A schedule will be posted here as it is developed.

Sponsors and Sponsorships

CCG is generously sponsoring a conference dinner. Thank you, CCG! Schrödinger is sponsoring our poster session, with food and drinks. Thank you, Schrödinger! The Laufer Center at Stony Brook University is also providing financial support for the meeting. Thank you, Laufer Center!

If your organization is interested in sponsoring, please contact David Mobley.

Support

Contact for travel arrangements, lodging, and general questions about Cambridge: Richard Dixon, Vertex Pharmaceuticals email (CC D. Mobley)

Date and Location

May 21-23, 2012
675 Kendall St [info | parking | directions | Google maps]
Cambridge, MA

Meeting room details will be announced.

The conference site will have wireless internet access via a guest password.

Fees

There is no registration fee for this workshop.

Workshop Format

There will be a number of talks with ample time for discussion. We hope to draw talks on several main themes, including (1) use cases for free energy techniques in real-world problems where they can or have had an impact; (2) how pharma can benefit today or in the immediate future; (3) parameterization and how the latest innovations here affect free energies; and (4) good sampling practices and challenges facing sampling and their impact on free energy estimates. Talks should be focused on addressing these or related aims. As in our previous workshop, participants should feel free to discuss work that highlights problems or limitations, present ideas on how these limitations may be overcome, and discuss new developments that are underway. Discussion of failures are encouraged!

Deadlines

  • Participants who are interested in speaking should contact us (the organizers) by Dec. 16, 2011.
  • Those wishing to attend should contact us as soon as possible (space is limited) but no later than Jan. 17, 2010. Additional spots may become open later. Registration is available via a web form at this link.

Lodging and meals

  • Coffee, lunch, and beverages will be provided at Vertex.
  • A conference dinner is generously being sponsored by CCG and the Laufer Center for Quantitative Biology.
  • Vertex has arranged for a block of rooms at a discounted rate ($179 per night plus tax), at the Hyatt Cambridge about 2 miles from the meeting:
  Hyatt Regency Cambridge
  575 Memorial Drive,
  Cambridge, Massachusetts, USA 02139-4896

For reservations, please call Vertex Travel: 

  Reservations can be made by calling Vertex travel -- as soon as possible as rooms may sell out
  617-444-6225 
  Please reference "Dixon - ENERGY"
  Reservations must be made at the time of the call.
  Reservations will be made using each individual's Credit Card account number.
  Anyone using this option will be responsible for all fees and/or cancellation or no-show penalties if incurred.
  Cancellation policy is 30 days prior to arrival -- by calling the hotel directly. (This unusual cancellation policy is apparently due to commencement season).

Schedule

A tentative draft schedule follows. Normal talks are 25 minutes + 5 minutes for questions. Some slots for short talks are available; these are 15 minutes + 5 minutes for questions.

Monday, May 21

Monday morning: 

 "War games: Model systems"
  David Mobley, moderator
    7:45-8:15: Coffee and pastries
    8:15-8:30: Opening remarks (Vertex?)
    8:30-9: Anita de Ruiter [ 25 min ] - "Efficient and accurate free energy calculations on trypsin inhibitors"
    9-9:30: Gabriel Rocklin  [ 25 min ] - "Testing alchemical free energy calculations in a charged model site"
    9:30-9:50: Coffee break [ 20 min ]
    9:50-10:20: Hari Muddana [ 25 min ] - "Binding affinities of host-guest systems using QM energy models"
    10:20-10:50:  John Chodera  [ 25 min ] - "Redesigning drug design"
    10:50-11:10: Coffee break [ 20 min ]
    11:10-11:40:  Richard Dixon [ 25 min ] - "Vertex sets for method testing"
    11:50-12: David Mobley - moderated discussion

Lunch at Vertex: 12-1

Monday afternoon: 

 "Validation and application"
  John Chodera, moderator
    1-1:30: Michael Shirts [ 25 min ] - "Validation efforts and efficiency improvements in free energy calculations"
    1:30-2: Clara Christ  [ 25 min ] - "Free energy calculations as a tool in drug discovery"
    2-2:20: Coffee break [ 20 min ]
    2:20-2:50: Marc Bianciotto [ 25 min ] - "Determination of the mode of action of FGFR ECD allosteric modulators"
    2:50-3:20:  Julien Michel [ 25 min ] - "Challenges and bottlenecks in applying free energy calculations in structure-based drug design"
    3:20-3:40: Coffee break [ 20 min ]
    3:40-4:10: Gianni de Fabritiis  [ 25 min ] - "Fragment-based drug design using molecular dynamics"
    4:10-4:30: John Chodera - moderated discussion
    4:30-4:50: Short talk 1 (TBA) [ 15 min ]
    4:50-5:10: Short talk 2 (TBA) [ 15 min ]

Conference dinner at ___ p.m.

Tuesday, May 22

Tuesday morning: 

 "Parameterization, force fields, and methodology"
  Vijay Pande, moderator
    7:45-8:30: Coffee and pastries
    8:30-9: Charles L. Brooks, III [ 25 min ] - TBA
    9-9:30: David A. Case [ 25 min ] - "Using free energy to update force fields" 
    9:30-9:50: Coffee break [ 20 min ]
    9:50-10:20: Daniel Zuckerman [ 25 min ] - "Simultaneous determination of equilibrium and non-equilibrium properties from the weighted ensemble (WE) method"
    10:20-10:50: Michael Schnieders [ 25 min ] - "Accelerating polarizable multipole AMOEBA free energy calculations using orthogonal space methods"
    10:50-11:10: Coffee break [ 20 min ]
    11:10-11:40:  Emilio Gallicchio [ 25 min ] - "Binding pathways, conformational sampling, and convergence: the shortest route is often not the fastest"
    11:50-12: Vijay Pande - moderated discussion

Lunch at Vertex: 12-1

Tuesday afternoon: 

 "You mean, we can use free energies for other things, too? Bound waters, permeation, and solubilities"
 Kim Branson, moderator
    1-1:30: Jonathan Essex [ 25 min ] - "Free energy calculations of the role of bound water in protein-ligand association"
    1:30-2: Guanglei Cui [ 25 min ] - "SPAM: a simple approach of profiling bound water molecules and its application in lead optimization"
    2-2:20: Coffee break [ 20 min ]
    2:20-2:50: Jean-Francois Truchon [ 25 min ] - "What can we learn from integral equation theory: Using 3D-RISM free energies in modeling"
    2:50-3:20:  Rommie Amaro [ 25 min ] - "Small molecule membrane permeability"
    3:20-3:40: Coffee break [ 20 min ]
    3:40-4:10:  Andrew Paluch [ 25 min ] - "Solubility prediction using free energy calculations and thermodynamic modeling"
    4:10-4:30: Kim Branson - moderated discussion
    4:30-4:50: Short talk 1 (TBA) [ 15 min ]
    4:50-5:10: Short talk 2 (TBA) [ 15 min ]

Poster session, mixer, and food -- Vertex lobby

Wednesday, May 23

Wednesday morning: 

 "Relative free energy calculations"
  Michael Shirts, moderator
    7:45-8:30: Coffee and pastries
    8:30-9:  [ 25 min ] - ""
    9-9:30:  [ 25 min ] - 
    9:30-9:50: Coffee break [ 20 min ]
    9:50-10:20: [ 25 min ] - ""
    10:20-10:50: [ 25 min ] - ""
    10:50-11:10: Coffee break [ 20 min ]
    11:10-11:40:  [ 25 min ] - ""
    11:50-12: Michael Shirts - moderated discussion

Lunch at Vertex: 12-1

Wednesday afternoon: 

 "Proteins aren't rocks -- they wiggle! Conformational changes and non-alchemical approaches"
 Richard Dixon, moderator
    1-1:30:  [ 25 min ] - ""
    1:30-2:  [ 25 min ] - ""
    2-2:20: Coffee break [ 20 min ]
    2:20-2:50:  [ 25 min ] - ""
    2:50-3:20:   [ 25 min ] - ""
    3:20-3:40: Coffee break [ 20 min ]
    3:40-4:10:   [ 25 min ] - ""
    4:10-4:30: Richard Dixon - moderated discussion
    4:30-4:50: Short talk 1 (TBA) [ 15 min ]
    4:50-5:10: Short talk 2 (TBA) [ 15 min ]

Speakers

Titles/topics listed when available

  • Abel, Robert (Schrödinger) -- "Relative binding free energy calculations for medicinally interesting targets including comparisons with alternative approaches"
  • Amaro, Rommie (University of California, San Diego) -- "Small molecule membrane permeability"
  • Bianciotto, Marc (Sanofi-Aventis) -- "Determination of the Mode of action of FGFR ECD allosteric modulators"
  • Brooks III, Charles L. (University of Michigan)
  • Bucher, Denis (University of California, San Diego) -- "Using Accelerated MD to Characterize Long Time-Scales in Proteins and Estimate the Reorganization Free energy upon Ligand Binding"
  • Case, David (Rutgers) -- "Using free energy calculations to update force fields"
  • Christ, Clara (Boehringer-Ingelheim) -- "Free energy calculations as a tool in drug discovery"
  • Chipot, Christophe (University of Illinois, Urbana-Champaign) -- "Calculations of standard binding free energies using adaptive biasing forces"
  • Chodera, John (University of California, Berkeley) --
  • Cui, Guangli (Glaxo-Smith-Kline) -- "SPAM: a simple approach of profiling bound water molecules and its application in lead optimization"
  • De Fabritiis, Gianni (Universitat Pompeu Fabra) -- "Fragment-based drug design using molecular dynamics"
  • de Ruiter, Anita (BOKU, Vienna) -- "Efficient and Accurate Free Energy Calculations on Trypsin Inhibitors"
  • Dixon, Richard (Vertex) -- "Vertex data sets for method testing"
  • Essex, Jonathan (University of Southampton) -- "Free energy calculations of the role of bound water in protein-ligand association"
  • Gallicchio, Emilio (Rutgers) -- "Binding pathways, conformational switching, and convergence: the shortest route is often not the fastest"
  • Michel, Julien (University of Edinburgh) -- "Challenges and Bottlenecks in Applying Free Energy Calculations in Structure-Based Drug Design"
  • Mobley, David (University of New Orleans) -- "Planning and conducting relative free energy calculations -- automation and issues"
  • Muddana, Hari (University of California, San Diego) -- "Binding affinities of host-guest systems using QM energy models"
  • Paluch, Andrew (University of Notre Dame) -- "Solubility prediction using free energy calculations and thermodynamic modeling"
  • Pande, Vijay (Stanford University) -- "Combining Markov State Models with Free Energy Calculations for Allostery"
  • Purisima, Enrico (National Research Council, Canada) -- "Binding entropy from exhaustive docking and conformational sampling and quasi-Newton Hessian approximation"
  • Rocklin, Gabriel (University of California, San Francisco) -- "Testing alchemical free energy calculations in a charged model site"
  • Schnieders, Michael (UT Austin) -- "Accelerating polarizable multipole AMOEBA free energy calculations using orthogonal space methods"
  • Shirts, Michael (University of Virginia) -- "Validation efforts and efficiency improvements in free energy calculations"
  • Truchon, Jean-Francois (Chemical Computing Group) -- tentatively, "What Can We Learn from Integral Equation Theory: Using 3D-RISM Free Energies in Modeling"
  • Van Gunsteren, Wilfred (ETH Zurich) -- "Methodological advances in the computation of relative free energies"
  • Wang, Lingle (Schrödinger) -- "Combination of enhanced sampling techniques into FEP to get structural reorganization effects in relative binding affinity calculations"
  • Woolf, Tom (Johns Hopkins) --
  • Zuckerman, Daniel (University of Pittsburgh) -- "Simultaneous determination of equilibrium and non-equilibrium properties from the weighted ensemble (WE) method"

Non-speaking attendees (poster presenters indicated)

  • Allen, William (Stony Brook University) Poster
  • Branson, Kim (Discovery Engine)
  • Brown, Scott (Sunivion). Poster
  • Cerutti, David (Rutgers) Poster
  • Cheng, Alan (Amgen) Poster
  • Cheng, Chia-en (University of California, Riverside) Poster
  • Cuendet, Michel (New York University) Poster
  • Deng, Nanjie (Rutgers)
  • Denny, R. Aldrin (Pfizer)
  • Dill, Ken A. (Stony Brook University)
  • Fochtman, Brian (Stony Brook University) Poster
  • Fujitani, Hideaki (University of Tokyo)
  • Gao, Chunxia (University of Gothenburg) Poster
  • Gao, Cen (Eli Lilly)
  • Hempel, Judith (Duke University)
  • Hidresh, Kumar (IIT, Delhi, India) Poster
  • Huang, Yulin (Stony Brook University) Poster
  • Jiang, Lingling (Stony Brook University) Poster
  • Kim, Byungchan (Schrodinger)
  • Kokubo, Hironori (Takeda Pharmaceutical Company) Poster
  • Kumar, Hirdesh (Indian Institute of Technology) Poster
  • Lamb, Michelle (AstraZeneca)
  • Lawrenz, Morgan (Stanford University) Poster
  • Lin, Teng (Schrödinger)
  • Mahboobi, S. Hanif (Berkeley) Poster
  • Okada, Okimasa (Mitsubishi Tanabe Pharma) Poster
  • Paluch, Andrew (University of Notre Dame) Poster
  • Parameswarn, Sreeja (University of New Orleans) Poster
  • Paulino, Margot (UdelaR) Poster
  • Rizzo, Robert (Stony Brook University) Poster
  • Sanders, Jeffrey (Thomas Jefferson University) Poster
  • Shams, Hengameh (Berkeley) Poster
  • Shi, Yue (University of Texas, Austin)
  • Shriram, Purohit (S.E.T. College of Pharmacy, Dharwad, India) Poster
  • Singh, Rajesh (Niper, India) Poster
  • Stouch, Terry (Science for Solutions, LLC) Poster
  • Swift, Robert (University of California, San Diego) Poster
  • Tsui, Vickie (Genentech)
  • Wickstrom, Lauren (Rutgers) Poster
  • Wu, Yujie (Schrödinger)
  • Zheng, Zhong (St. Jude Children's Research Hospital) Poster
  • Zunini, Margot Paulino (Universidad de la República, Uruguay) Poster

Restaurants in Boston

Cambridge Restaurants

Directions from Cambridge to Boston

MBTA: Red Line from Kendall to MGH (one stop) takes you to the top of Charles Street, the Liberty Hotel, and the Beacon Hill neighborhood of Boston. In Boston, continuing on the Red Line one additional stop to Park Street is the connection to the Green Line. Inbound one stop on the Green Line is Government Center – a short walk from there to Faneuil Hall. Outbound on the Green Line from Park Street Station will take you to the Back Bay neighborhood – Arlington & Copley Square stations. All of this from Park Street is also very walkable above ground. A quick cab or a 15 minute stroll south of Back Bay (down Clarendon Street is one route) takes you to the South End neighborhood.

Beacon Hill Restaurants

Back Bay Restaurants

South End Restaurants

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