2014 Workshop on Free Energy Methods in Drug Design

This conference is in the active planning stage; please check back regularly for additional information!

The 2014 Workshop on the State of Free Energy Calculations in Drug Design
Dates: May 19th-21st, 2014
Venue: Vertex Pharmaceuticals, Boston, MA (Fan Pier location)

Introduction

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 as organizers believe that these techniques are even closer than before to making an impact in appropriate drug discovery applications, by allowing physics-based prediction of physical properties such as binding affinity, selectivity, solubility, and membrane permeability. However, a number of challenges still 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.

Organizers

• Kim Branson, Hessian Informatics email
• John Chodera, Memorial-Sloan Kettering Cancer Center email
• Richard Dixon, Vertex email
• David Mobley, University of California-Irvine email
• Vijay Pande, Stanford University email
• Michael Shirts, University of Virginia email

Differences from previous workshops

We are hosting the workshop in a new venue: Vertex's auditorium in Boston, rather than at the Cambridge site. This means:

• More room. Although the number of speakers will not change, the number of participants will be able to expand to approximately 90.
• No confidentiality agreements. The auditorium is outside the "protected zone", which should hopefully allow a much bigger range of speakers.
• We are also making a bigger effort to get more industry participation, with a goal that at least 1/3 of the talks are from industrial researchers.

Workshop format

There will be a number of talks spaced over three days, 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 best benefit today or in the immediate future;
3. Parameterization of small molecules and proteins and how the latest innovations here affect free energies;
4. Good sampling practices and challenges facing sampling and their impact on free energy estimates, and
5. Design of experimental and simulation studies that could directly demonstrate the utility of free energy calculations in widespread industrial use.

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.

Preliminary Schedule

Monday, May 19

Monday morning:

 "Large scale free energy calculations"
    8:00-8:30: Coffee and pastries
    8:30-8:45: Welcome and Opening remarks 
    8:45-9:15: Jose Duca - TBA
    9:15-9:45: Ron Levy - "Binding Free Energies  on a Large Scale and Replica Exchange Sampling"
    9:45-10:05: Coffee break  
    10:05-10:35: Alan Mark - "Single step perturbation approaches in ligand design and force field parameterization"
    10:35-11:05 Robert Abel - "Binding affinities of host-guest systems using QM energy models"
    11:05-11:35: Clara Christ - "Free energy calculations – soon a standard tool in drug design?"
    11:35-11:50: Floris Beulens - “Comparing Relative and Absolute Binding Free Energy Calculations for Inhibitors of Kinase PDK1”
    
    11:50-1:30: Lunch (at Vertex)
    12:30-1:30: Moderated lunchtime discussion (topics TBA)

Monday Afternoon

"And now for something completely different: Free energy alternatives to ‘alchemical’ calculations"
    1:30-2:00 Marti Head - TBA
    2:00-2:30 Enrico Purisima - TBA
    2:30-2:50 Coffee
    2:50-3:20 Gianni di Fabriitis - "In-silico ligand binding assays: poses, affinities and kinetics"
    3:20-3:50 Riccardo Baron -  TBA
    3:50-4:10 Coffee
    4:10-4:40 Vijay Pande - "What should we be predicting?   Some arguments on where computation could be best applied in computational drug design and some new methods to do it"
    4:40-4:55 Gaetano Calabro - "Investigation of Non-Additivity in Protein-Ligand Binding"
    4:55-5:30 Moderated discussion and daily wrap-up

Tuesday, May 20

Tuesday Morning

    "I seen a lot in my time: Conformational sampling"
    8:00-8:30: Coffee and pastries
    8:30-9:00 Charlie Brooks - TBA
    9:00-9:30 Wei Yang - "Receptor-Ligand Binding Prediction in Explicit Solvent Environment"
    9:30-9:50 Coffee
    9:50-10:20 Michael Shirts - TBA
    10:20-10:50 David Minh - “Protein-Ligand Binding Free Energies using Implicit Ligand Theory”
    10:50-11:10: Coffee
    11:10-11:40 Emilio Gallichio - “Extending Binding free energy calculations to large, flexible molecules”
    11:40-11:55 Daniel Cole - “Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering”

    11:55-1:30 Lunch (at Vertex)
    12:30-1:30 Moderated lunchtime discussion (topics TBA)

    Tuesday afternoon
    "Dotting the i’s and crossing the t’s: Making free energy calculations robust"
    1:30-2:00 Benoit Roux: "Electrostatics and absolute free energies of charged species”
    2:00-2:30 David Mobley: “Using solution-phase free energy calculations to improve binding free energies"
    2:30-2:50 Coffee 
    2:50-3:20 Chris Oostenbrink - "Binding free energy calculations involving a net charge change"
    3:20-3:50 Lingle Wang -  "Important components in making FEP work"
    3:50-4:10 Coffee
    4:10-4:40 Huafeng Xu - TBA
    4:40-4:55 Gabe Rocklin: “How to accurately correct for periodicity artifacts in protein-ligand binding calculations on charged compounds”
    4:55-5:30 Moderated discussion and daily wrap-up

Wednesday, May 21

  Wednesday morning
  "Free energy calculations: Not just  for binding any more!"

    8:00-8:30: Coffee and pastries
    8:30-9 Pat Walters - TBA
    9:00-9:30 Chris Chipot - "Determination of lipid-bilayer permeabilities from first principles"
    9:30-9:50 Coffee
    9:50-10:20 Mike Schnieders - "Molecular Design Using Many-Body Physics"
    10:20-10:50 JW Feng - TBA
    10:50-11:10: Coffee
    11:10-11:40 Chris Bayly - TBA
    11:40-11:55 Chris Neale - “Identifying Hidden Free Energy Barriers"

    11:55-1:30 Lunch (at Vertex)
    12:30-1:30: Moderated lunchtime discussion (topics TBA)

   Wednesday afternoon
   "Representing the system: Waters and force fields"
    1:30-2:00 Bernie Brooks: “Recent advances in hybrid quantum-chemical approaches for free energy simulations and constant pH simulations”
    2:00-2:30 Paul Czodrowski - “From H to O to H2O”
    2:30-2:50 Coffee
    2:50-3:20 Pengyu Ren - TBA
    3:20-3:50 Lars Sandberg - “Let’s be explicit about implicit solvent models”
    3:50-4:10 Coffee
    4:10-4:40 John Chodera- “Collecting the data we need to make progress”
    4:40-4:55 Gregory Ross - “Automated inclusion of water in alchemical free energy calculations for drug-protein complexes"
    4:55-5:30 Moderated discussion and daily wrap-up, and conference farewell

Participation

Event registration is now closed, as the event is filled to capacity, and speaking slots are filled. If there are particular compelling reasons that you should attend, please contact Michael Shirts (michael.shirts@virginia.edu).

Confirmed Speakers

• Robert Abel, Schrodinger
• Riccardo Baron, U. of Utah
• Chris Bayly, OpenEye
• Charlie Brooks, U. of Michigan
• Christoph Chipot, U. of Illinois
• Clara Christ, Bayer
• John Chodera, Memorial-Sloan Kettering Cancer Center
• Paul Czodrowski, Merck Darmstadt
• Gianni de Fabritiis, Universitat Pompeu Fabra
• Jose Duca, Novartis
• JW Feng, Genentech
• Emilio Gallicchio, CUNY-Brooklyn
• Marti Head, GSK
• Ron Levy, Rutgers
• Alan Mark, U. Queensland
• David Minh, Illinois Institute of Tech.
• David Mobley, U. of California-Irvine
• Chris Oostenbrink, University of Natural Sciences and Life Sciences, Vienna
• Vijay Pande, Stanford
• Enrico Purisima, National Research Council Canada
• Pengyu Ren, U. of Texas
• Benoit Roux, U. of Chicago
• Lars Sandberg, U. of Dundee
• Michael Shirts, U. of Virginia
• Mike Schnieders, U. of Iowa
• Lingle Wang, Schrodinger
• Pat Walters, Vertex
• Huafeng Xu, D. E. Shaw Research
• Wei Yang, Florida State

Registration, lodging and meal costs

There is no registration fee. We regret that we are unable to provide funding for travel and lodging at this time. Vertex travel has agreed to help people find housing in the Boston area with a Vertex corporate discount. You can email VertexTravel@aexp.com to get assistance in booking a hotel room with this discount. They know to expect you: mention the Workshop on the State of Free Energy Calculations in Drug Design on May 19th - 21st.

Breakfast, lunch, and coffee will be provided at the venues on the days of the conference. Schrodinger will be sponsoring refreshments for a poster session one evening, and we are recruiting sponsors for a group dinner another evening (Open Eye is participating, we are looking for others). If your organization is interested in sponsoring, please contact Michael Shirts (michael.shirts@virginia.edu).