2010 Workshop on Free Energy Methods in Drug Design

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2010 Workshop on Free Energy Methods in Drug Design

May 17-19, Cambridge, Massachusetts, USA


Since their first application decades ago, free energy methods have promised great potential for revolutionizing the process of drug discovery. Recent advances in computational power, new efficient algorithms, and forcefield development efforts suggest that this potential could soon be realized, but there remains a 'last mile' problem in bringing these powerful techniques to the point where they can play a significant role in driving drug discovery in both pharma and academia.

To identify the remaining challenges and help foster a concerted effort to overcome them, we are organizing an intense workshop devoted to bringing together experts from pharma and supporting industries, as well as from academia. The emphasis of this workshop will be on identifying current challenges in the drug discovery process -- specifically those where free energy methods might have the most impact -- and determining the work that must be done as a community to make free energy methods usable for these purposes.


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


Contact for travel arrangements, lodging, and general questions about Cambridge:

  • Vicki McKinnon, Vertex Pharmaceuticals email

Date and Location

May 17-19, 2010
675 Kendall St [info | parking | directions | Google maps] (Kendall Lecture Hall, 3rd floor)
Cambridge, MA

The meeting will take place in the Kendall Lecture Hall in the Vertex space on the third floor of 675 West Kendall.

On entering 675 West Kendall Street, there will be a sign-in table in the main lobby. After signing in and receiving a Visitor Pass, take the elevator to the third floor. There will be a security officer at the elevators on the third floor who will check your Visitor Pass. Proceed to the Kendall Lecture Hall, located inside the Vertex space and to the right.

Passes should be relinquished on leaving Vertex each evening.

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


There is no registration fee for this workshop.

Workshop Format

There will be a number of talks with ample time for discussion. The workshop will be highly focused on (1) identifying the particular opportunities where free energy methods can have an impact on drug discovery, (2) enumerating the challenges remaining before free energy methods can find widespread use in ligand and drug design, and (3) facilitating the organization of 'working groups' to aid in tackling various aspects of these challenges after the meeting has concluded. Talks should be focused on addressing these (or related) aims. For example, 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!

Three kinds of presentations will be available, with ample time for discussion allotted.

  • 25-minute talks to highlight some of the above issues encountered in work or present new tools
  • 10-minute talks to give brief updates on projects or inspire discussion about questions
  • poster presentations (encouraged for attending students or highlighting issues or methods in more detail)



Lodging and meals

  • Coffee, lunch, and beverages will be provided at Vertex.
  • A conference dinner will be held at the Cambridge Brewing Company on Monday, 17 May at 6.30 pm. We have not found a sponsor for this dinner, so individuals will have to pay for their own meals and attendance is optional.
  • We regret that we are unable to provide funding for travel and lodging, but you may use the Vertex Transient Room Rate at the Royal Sonesta Hotel, Cambridge, MA (yelp | tripadvisor), close to Vertex (Vertex is located at 675 W Kendall St.)
 The Royal Sonesta Hotel
 40 Edwin Land Boulevard
 Cambridge, MA 02142

Please request the VERTEX RATE covering any combination of the nights of May 16 – May 19 inclusive:

 STANDARD ROOM: $185 + tax per room per night.
 DELUXE ROOM (view of the Charles River): $235 + tax per room per night.  

May is high season in Boston and Cambridge (tourists, graduations, etc.) so please call and make your reservations as soon as possible.

To make a reservation using the VERTEX RATE:

 Call the Royal Sonesta Hotel direct 617-806-4200; or
 Call the Vertex Travel Dept: 617-44-6225; or
 Have your travel agency book the VERTEX RATE. 

Cancellation policy for The Royal Sonesta Hotel is:

 By 6 PM, 24 hours prior to date of arrival. 

The hotel is a 7-12 minute walk to the Vertex site. The hotel can provide complimentary shuttle service, so please inquire at GUEST SERVICES for available times to use the 14-passenger van to the meeting.


Talk abstracts can be found here.

Monday 17 May

Monday morning - perspective from pharma
"If we could do this, would it matter anyway? Or should we all go work for the finance industry?"
Kim Branson, moderator
 7.45- 8.15 coffee and pastries
 8.15- 8.30 Kim Branson (Vertex) [10 min] - introductory remarks
 8.30- 9.05 Mark Murcko (Vertex) [25 min] - TBA
 9.05- 9.40 Scott Brown (Abbott) [25 min] - What does it take to positively impact industrial drug design?
 9.40-10.00 coffee break [20 min]
10.00-10.35 Dan Price (GSK) [25 min] - TBA
10.35-10.50 John Van Drie (Van Drie Research LLC) [10 min] - How can imperfect free-energy methods best impact drug discovery?
10.50-11.10 coffee break [20 min]
10.10-11.45 Terry Stouch [25 min] - Particulars and concerns regarding the accuracy and precision of force field calculated energies
11.45-12.00 Kim Branson - moderated discussion

12.00- 1.00 lunch at Vertex

Monday afternoon - "What could possibly go wrong?" - Challenges in free energy calculations
David Mobley (University of New Orleans), moderator

 1.00- 1.15 David Mobley [10 min] - introductory remarks  
 1.15- 1.50 Julien Michel (Yale) [25 min] - Water in binding free energy calculations 
 2.50- 2.25 Richard Dixon [25 min] - Antechamber: The sequel 
 2.25- 2.45 coffee break [20 min]
 2.45- 3.15 William Swope [20 min] - What is state of the art in hydration free energy computations?
 3.15- 3.45 Julia Rice [20 min] - Can we develop better charges for fixed charge force fields?
 3.45- 4.00 coffee break [15 min]
 4.00- 4.35 Wei Yang (FSU) [25 min] - High-order generalized ensemble theory enables the sampling of long-timescale events for free energy simulations
 4.35- 4.55 David Case [10 min] - Free energy methods in Amber and DOCK [10 min]
 4.55- 5.30 Woody Sherman (Schrodinger) [25 min] - Predicting relative binding free energies with FEP: Large-scale validation and parameter optimization study on pharmaceutically relevant targets
 5.30- 6.00 David Mobley - moderated discussion
 6.30- 8.30 dinner at Cambridge Brewing Company, 1 Kendall Square Bldg. 100 [15 min walk from Vertex]

Tuesday 18 May

Tuesday morning - "Tales from the trenches" - Current results from free energy calculations  
Michael Shirts, moderator

 7.30- 8.00 coffee and pastries

 8.00- 8.15 Michael Shirts [10 min] - introductory remarks
 8.15- 8.50 Derek Lowe (Vertex) [25 min] - Perspectives from "In the Pipeline"
 8.50- 9.25 Jonathan Essex (University of Southampton) [25 min] - "Rigorous free energy calculations - a personal perspective on what does and does not work" 
 9.25- 9.45 coffee break [20 min]
 9.45-10.20 Julian Tirado-Rives (Yale) [25 min] - Successes and Challenges for FEP-Guided Optimization of Enzyme Inhibitors
10.20-10.55 Hideaki Fujitani (University of Tokyo) [25 min] - MP-CAFEE: principles and challenges
10.55-11.10 coffee break [15 min]
11.10-11.45 Pengyu Ren (UT Austin) [25 min] - Free Energy Calculations using Polarizable Multipole-based AMOEBA Potential 
11.45-12.00 Michael Shirts - moderated discussion

12.00- 1.00 lunch at Vertex

Tuesday afternoon - "Zen and the Art of Free Energy Calculations" - unconventional approaches  
Vijay Pande, moderator
 1.00- 1.15 Vijay Pande [10 min] - introductory remarks
 1.15- 1.50 Christopher Bayly (Merck Frosst) [25 min] - Trying to Avoid Free Energy Calculations using MMPBSA   
 1.50- 2.25 Enrico Purisima [25 min] - "The Usual Suspects"
 2.25- 2.45 coffee break [20 min]
 2.45- 3.20 Emilio Gallicchio (Rutgers) - The binding energy distribution analysis method (BEDAM): Theory and applications
 3.20- 3.40 David Minh [10 min] (ANL) - Nonequilibrium free energy methods in drug design
 3.40- 4.00 coffee break [20 min]  
 4.00- 4.35 Matt Clark (Pharmatrope) - Fast free energy calculation based on Monte Carlo sampling of pose and conformation with a flexible protein model
 4.35- 5.05 Rich Friesner [20 min] - TBA
 5.05- 5.20 Vijay Pande - moderated discussion 

Tuesday evening - poster session
 5.30- 7.30 poster session and drinks at Schrodinger
Hosted by Woody Sherman (Schrodinger)

* David Cerutti (Rutgers) - (space permitting)
* Mikolai Fajer (UCSD) - Combining Multistate Free Energy Methods with Replica Exchange Accelerated MD
* Morgan Lawrenz (UCSD) - Impact of calcium on N1 influenza neuraminidase dynamics and binding free energy
* David Minh (ANL) - Absolute Partition Functions without a Reference State
* Chris Neale (U Toronto)
* Gabriel Rocklin (UCSF)
* Michael Schnieders (Stanford) - Calculation of the thermodynamic properties of crystals (solubility and possibly polymorphs)
* Yi Wang (UCSD) - Expedited conformational space sampling with accelerated molecular dynamics in NAMD
* Jeff Wiseman (Pharmatrope) - Fast free energy calculation based on Monte Carlo sampling of pose and conformation with a flexible protein model
* Daniel Zuckerman - Symmetry of forward and reverse processes: Conditions and counter-examples

 7.00-  dinner on own in Cambridge

Wednesday 19 May

Wednesday morning - sampling, convergence, and error for free energy methods
John Chodera (UC Berkeley), moderator

 7.30- 8.00 coffee and pastries

 8.00- 8.15 John Chodera [10 min] - introductory remarks
 8.15- 8.50 Daniel Zuckerman (University of Pittsburgh) [25 min] - Judging biomolecular sampling, and achieving it with variable-resolution models
 8.50- 9.25 Sereina Riniker (ETH Zurich) [25 min] - Efficient computation of relative free energies using enveloping distribution sampling and one-step perturbation
 9.25- 9.45 coffee break [20 min]
 9.45-10.20 Régis Pomès (Hospital for Sick Children/University of Toronto)[25 min] - Efficient algorithms for conformational sampling in free energy simulations
10.20-10.35 Gerhard König (Universität Wien) [10 mins] - Comments on Free Energy Methods: Choosing one that fits your needs 
10.35-10.50 coffee break [15 min]
10.50-11.25 Harry Stern [25 min] - Conformational restriction, multiple protonation states, and polarization in protein-ligand binding
11.25-12.00 Jeff Wereszczynski (UCSD) [25 min] - Using Accelerated Molecular Dynamics to Enhance Free Energy Calculations

12.00- 1.00 lunch at Vertex

Wednesday afternoon - best practices and physical phenomena   
Michael Shirts (University of Virginia), moderator

 1.00- 1.35 Huafeng Xu (DESRES) [25 min] - Reducing statistical errors in free energy calculations
 1.35- 2.10 Andrew Pohorille (NASA AMES) [25 min] - Good practices in free energy calculations
 2.10- 2.25 coffee break [15 min]
 2.25- 3.00 Tom Woolf (Johns Hopkins) [25 min] - Finding, binding and analyzing transition intermediates: How we might define new drug targets[10 min] 
 3.00- 3.15 Marcus Weber [10 min] - Simulation of binding kinetics using a transfer operator approach
 3.15- 3.40 Fernando Escobedo (Cornell) [25 min] - On the coupling of simulations of free energy and transitional kinetics
 3.40- 4.00 coffee break [20 min]
 4.00- 4.35 Thomas Simonson, Ecole Polytechnique, France [25 min] - Probing charge interactions with free energy simulations
 4.35- 5.00 closing remarks


  • Christopher Bayly, Merck-Frosst
  • Kim Branson, Vertex
  • Scott Brown, Abbott
  • David Case, Rutgers
  • Matthew Clark, Pharmatrope
  • John Chodera, UCB
  • Richard Dixon, Vertex
  • John Van Drie, Van Drie Research LLC
  • Fernando Escobedo, Cornell
  • Jonathan Essex, University of Southampton
  • Rich Friesner, Columbia
  • Hideaki Fujitani, University of Tokyo
  • Emilio Gallicchio, Rutgers University – BioMaPS Institute
  • Julian Tirado-Reves, Yale
  • Gerhard König (Boresch group), Universität Wien
  • Derek Lowe, Vertex
  • Julian Michel (Joregensen group), Yale
  • David Minh, Argonne National Laboratory
  • David Mobley, UNO
  • Mark Murcko, Vertex
  • Vijay Pande, Stanford
  • David Pearlman, Dapper Research
  • Daniel Price, GSK
  • Andrew Pohorille, NASA AMES
  • Régis Pomès, Toronto
  • Enrico Purisma, NRC-BRI
  • Pengyu Ren, UT Austin
  • Julia Rice, IBM Alamden
  • Sereina Riniker (van Gunsteren's group), ETH Zurich
  • Woody Sherman, Schrodinger
  • Michael Shirts, UVa
  • Thomas Simonson, Ecole Polytechnique, France
  • Harry Stern, University of Rochester
  • Terry Stouch, Science for Solutions LLC
  • William Swope, IBM Almaden
  • Marcus Weber, Zuse Institute Berlin
  • Jeff Wereszczynski (from McCammon group), UCSD
  • Tom Woolf, Johns Hopkins University
  • Huafeng Xu, DESRES
  • Wei Yang, FSU
  • Dan Zuckerman, U Pittsburgh

Non-speaking attendees

  • Pavel Klimovich (Mobley lab), UNO
  • Gabriel Rocklin (Dill lab), UCSF
  • Pat Walters, Vertex
  • Yi Wang (from McCammon group), UCSD
  • Devleena Shivakumar, Schrodinger
  • Yujie Wu, Schrodinger
  • Kathryn Loving, Schrodinger
  • Mike Schnieders, Stanford
  • Chris Neale, University of Toronto
  • Jeff Wiseman, Pharmatrope
  • Tom Darden, OpenEye
  • Mikolai Fajer (McCammon group), UCSD
  • Paula Petrone, Novartis
  • Morgan Lawrenz (McCammon Group), UCSD
  • Viktor Hornak, Merck
  • Johnny Wu (Ren group), UT Austin
  • Jiajing Zhang (Ren group), UT Austin
  • Mauro Lapelosa (Levy group), Rutgers
  • Dave Cerutti (Case group), Rutgers
  • Demetri Moustakas
  • Marti Head, GSK
  • Ben Sellers, Genentech
  • Robert Abel, Schrodinger
  • Kwangho Nam, Karplus group

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