2016 Workshop on Free Energy Methods in Drug Design: Targeting Cancer

The 2016 Workshop on Free Energy Calculations in Drug Design: Targeting Cancer
Dates: May 16th-18th, 2016
Venue: Auditorium of Building 1, Vertex Pharmaceuticals Headquarters, Boston, MA
50 Northern Avenue Boston, MA 02210

The Vertex Workshop will be followed by a Markov State Modeling (MSM) Workshop at Novartis
Dates: May 19th-20th, 2016

We would like to thank the following sponsors:

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

• John Chodera, Memorial-Sloan Kettering Cancer Center (john.chodera@choderalab.org)
• Brian McClain, Vertex Pharmaceuticals (brian_mcclain@vrtx.com)
• Michael Schnieders, The University of Iowa (michael-schnieders@uiowa.edu)

We also recognize previous organizers and current advisors

• David Mobley, University of California at Irvine (dmobley@uci.edu)
• Vijay Pande, Stanford University (pande@stanford.edu)
• Michael Shirts, University of Virginia (michael.shirts@virginia.edu)
• Camilo Velez-Vega, Entasis Therapeutics (camilo.velez@entasistx.com)

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. Application of Free Energy Methods to New and Established Cancer Therapeutics
2. Optimization for Potency and/or Selectivity
3. Sensitivity of Binding Results to Force Field, Sampling and Simulation Choices
4. Constant pH and Chemical Effects (i.e. Protomers and Tautomers) During Binding
5. Beyond Binding: Free Energy Calculations Throughout the Drug Discovery Pipeline
6. Predicting Resistance and Designing Biologics: Protein Mutational Free Energies
7. New or Enhanced Tools to Setup and Execute Successful Free Energy Calculations

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

The schedule below is in alphabetical order; as we receive all the talk titles the order will be re-arranged into sessions.

Monday, May 16th

• Keynote by Mark Murko on Monday morning.

• Robert Abel (Schrödinger): Accelerating drug discovery with free energy calculations
• Kira Armacost (C. Brooks Group at Michigan): Predicting binding free energies in a combinatorial chemical space using multisite lambda dynamics
• Christopher Bayley (OpenEye): Charge-ELF: Addressing conformational dependency of small-molecule atomic charges for biomolecular simulations
• Phil Biggin (Oxford): Ligand Selectivity Assessed by Absolute Free Energy Calculations
• Bernie Brooks (NIH): Recent advances in free energty methods and lessons learned from SAMPL5
• Christophe Chipot (U. of Illinois)
• Clara Christ (Bayer): Binding affinity prediction from molecular simulations. A new standard method in structure-based drug design?
• John Chodera (MSKCC): How can we best combine computation and experiment to move the field forward?
• Guanglei Cui / Eric Manas (GSK): Relative Binding Affinity Predictions: an Ongoing Evaluation of FEP+ at GSK
• Daan Geerke (VU University Amsterdam): Automated and efficient approaches for empirical binding free energy prediction from simulation, reliability estimation and model inference
• Emilio Gallicchio (Brooklyn College CUNY for 5/17 & 5/18): Alchemical Absolute Binding Free Energy Calculations for Peptide-Protein Complexes: Progress and Challenges

Tuesday, May 17th

• Michael Gilson (UCSD): Precise Calculation of Binding Thermodynamics for Model Systems
• JC Gumbart (Georgia Tech): MD-guided design of new inhibitors against Hepatitis B Virus
• Niels Hansen (Universität Stuttgart): Sensitivity of the standard binding free energy to the simulation set-up using the example of cyclodextrin-alcohol binding
• Jennifer Knight (Schrödinger): Advancing Free Energy Calculations in Real Time
• Ron Levy (Temple): Exploring Fitness and Free Energy Landscapes of Proteins for Allostery and Ligand Binding
• Frank Lovering (Pfizer): Free Energy Perturbation: Signals within the ‘Domain of Applicability’
• Alex MacKerell (U. of Maryland)
• Alan E. Mark (U. of Queensland): Free energy based automated force field refinement
• Yinglong Miao (McCammon Group at UCSD): Gaussian Accelerated Molecular Dynamics (GaMD): Unconstrained Enhanced Sampling and Free Energy Calculation
• Julien Michel (Edinburgh): Current limits of binding free energy calculations
• David Minh (IIT): Emerging methods for second-stage virtual screening
• David Mobley (UCI): Examining how protein sampling impacts the convergence of relative binding free energy calculations

Wednesday, May 18th

• Joe Morrone (Laufer Center): Modeling peptide-protein binding with information accelerated molecular dynamics
• Chris Oostenbrink (BOKU Vienna): Approximating robust free-energy methods using a small number of simulations
• Sereina Riniker (ETH Zurich): Improvements of Enveloping Distribution Sampling for Free Energy Calculation
• Benoît Roux (U. Chicago): Useful free energy computations: wrestling the beast
• Mike Schnieders (U. Iowa): Sampling approaches that accelerate free energy calculations from expensive force fields
• Jana Shen (U. of Maryland): Screening pH-dependent binding profiles of small-molecule inhibitors
• Michael Shirts (U. Colorado)
• Thomas Simonson (Ecole Polytechnique): Free energy simulations to design peptide binders and modulate the action of PDZ signaling domains
• Muneeb Sultan (Pande Group at Stanford): Markov Modeling of Protein Kinases
• Andreas Verras (Merck): Free energy calculations vs. less expensive scoring methods in the real world
• Huafeng Xu (D. E. Shaw Research): Alchemical free energy calculations of the binding affinity change associated with cyclization and functional group insertion
• Wei Yang (Florida State): Orthogonal space free energy sampling methods for drug discovery

Poster Session Sponsored by Schrödinger

The Poster Session, sponsored by Schrödinger, will again be held directly adjacent to the auditorium in a multipurpose conference room. Posters can be up to 48 inches wide. They will be placed on a fabric walls (with pushpins) and other walls (with fun-tak mounting putty), which will be provided. The poster session room will be directly adjacent to the conference room, and people can set up their posters during lunch or other breaks on Monday.

Travel and Lodging

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 vertex@us.fcm.travel or call at (877)-503-0771 or (781)-287-9136 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 16th - 18th.

If you are getting a hotel further out and driving in, parking information is available at http://en.parkopedia.com/parking/garage/fan_pier_garage/02210/boston/ and will range from $36 to $38 for the day depending on when you leave. If you are taking public transport, Fan Pier is on the Silver Line (a high-speed, dedicated lane bus line).

Coffee and pastries as well as lunch will be provided at the venues on the days of the conference, and there will be vegetarian options. Schrodinger will be sponsoring refreshments for a poster session Monday evening.

Participation

Event registration is now closed; registered participants are listed below. If you have a compelling reason to attend, but missed the registration period, please email Mike Schnieders (michael-schnieders@uiowa.edu).

Registered Conference Participants

• Robert Abel, Schrödinger
• Ameed Abualteen, New York U., Abu Dhabi
• Steven Albanese, MSKCC
• Matteo Aldeghi, U. of Oxford
• Armin Avdic, U. of Iowa
• Kira Armacost, U. of Michigan
• Eric Arnoult, Janssen Research & Development L.L.C.
• Julie Behr, MSKCC
• Jarod Benowitz, U. of Iowa
• Govinda Bhisetti, Biogen
• Phil Biggin, U. of Oxford
• Baofeng Zhang, Brooklyn College
• Denis Bucher, Galapagos
• Qing Cao, Astrazeneca
• Siqin Cao, Hong Kong U. of Science and Technology
• Navaneet Chaturved, Tel Aviv U., Israel
• Xin Chen, NIBR
• Franck Chevalier, Acellera
• Chris Chipot, CNRS/UIUC
• Clara Christ, Bayer Pharma AG
• Guanglei Cui, GSK
• Anita de Ruiter, BOKU, Vienna, Austria
• Callum Dickson, Novartis
• Xinqiang Ding, U. of Michigan
• Vicki Feher, U. of California, San Diego
• Philip Fowler, U. of Oxford
• Holly Freedman, Applied Virology Institute, University of Alberta
• Kyoto Fukushima, Japan Tobacco Inc.
• Emilio Gallicchio, Brooklyn College of CUNY
• Paul Gasper, U. at Albany SUNY
• Daan Geerke, VU University De Boelelaan
• Michael Gilson, U. of California, San Diego
• Andrei Golosov, Novartis
• Patrick Grinaway, MSKCC
• James Gumbart, Georgia Tech
• Kamran Haider, Lehman College, City U. of New York
• David Hall, Acpharis
• Niels Hansen, U. of Stuttgart, Germany
• Sonya Hanson, MSKCC
• Torsten Herbert, Forma Therapeutics
• Viktor Hornak, Novartis
• Rajeev Hotchandani, Scilligence
• Yuan Hu, Merck Research Laboratories
• Nadine Ibrahim, New York U., Abu Dhabi
• Christopher Ing, U. of Toronto
• Theresa Johnson, EMD Serono, Inc.
• Jordi Juárez-Jiménez, U. of Edinburgh
• Jarek Juraszek, Janssen Prevention Center
• Mitsunori Kato, Novartis Institutes for BioMedical Research
• Jennifer Knight, Schrodinger
• Daniel Kuhn, Merck
• Michelle Lamb, AstraZeneca R&D Boston
• David Langley, Bristol-Myers Squibb Co.
• Matthew Lardy, Genentech
• Ron Levy, Temple U.
• Jacob Litman, U. of Iowa
• Chen Li, Illinois Institute of Technology
• Qian Liu, Johnson & Johnson R&D, Shanghai
• Silvia Lovera, UCB Pharma
• Frank Lovering, Pfizer
• Rosa Luirink, VU University, Amsterdam
• Stephen LuCore, U. of Iowa
• Mark Murcko, Schrödinger
• Alex MacKerell, U. of Maryland, Baltimore
• Robert Malmstrom, U. California, San Diego
• Alan Mark, U. of Queensland
• Christian Mazza, U. of Fribourg
• Dan McKay, Novartis
• Antonia Mey, U. of Edinburgh
• Christophe Meyer, Johnson & Johnson
• Yinglong Miao, HHMI, U. of California, San Diego
• Julien Michel, U. of Edinburgh
• David Minh, Illinois Institute of Technology
• David Mobley, U. of California, Irvine
• Joseph Morrone, Stony Brook U.
• Naoki Nakao, Daiichi-Sankyo RD Novare
• Toan Nguyen, Astrazeneca
• Trung Hai Ngyuen, Illinois Institute of Technology
• Okimasa Okada, Mitsubishi Tanabe Pharma Corp.
• Chris Oostenbrink, U. of Natural Resources and Life Sciences
• Nilkanth Patel, Bridge Institute, U. of Southern California
• Anna Pavlova, Georgia Institute of Technology
• Janet Paulsen, U. of Massachusetts Medical School
• Guillermo Pérez-Hernández, Freie Universität Berlin
• Diego Prada-Gracia, Icahn School of Medicine at Mount Sinai
• Cristian Predescu, D. E. Shaw Research
• Ninad Prabhu, GSK
• Davide Provasi, Mount Sinai School of Medicine
• Shriram Purohit, S.E.T.'s College of Pharmacy, Dharwad, India
• Sereina Riniker, ETH Zurich
• Andrea Rizzi, MSKCC
• Michael Robertson, Yale
• Gregory Ross, MSKCC
• Bas Rustenburg, MSKCC
• Jeffrey Sanders, Schrodinger, Inc
• Michael Schnieders, U. of Iowa
• Simone Sciabola, Pfizer
• Jana Shen, U. of Maryland
• Bradley Sherborne, Merck
• Thomas Simonson, Ecole Polytechnique, Paris
• Laurentiu Spiridon, Illinois Institute of Technology
• Nathaniel Stanley, Stanford and Genentech
• Chaya Stern, MSKCC
• Mohammad Sultan, Stanford University
• Wenji Sun, Illinois Institute of Technology
• Xianqiang Sun, Washington University School of Medicine
• Kcnichiro Takaba, Asahi Kasei Pharma Corporation
• Torsten Herbertz, Forma Therapeutics
• Sweta Vangaveti, The RNA Institute, State University New York, Albany
• Camilo Velez, Entasis Therapeutics
• Andreas Verras, Merck
• Nadeem Vellore, Dart Neuroscience
• Jonah Vilseck, Yale University
• Ross Walker, U. of California, San Diego
• Patrick Walters, Relay Therapeutics
• Lingle Wang, Schrodinger
• Cody Weinberger, D. E. Shaw Research
• Thomas Weinreich, D. E. Shaw Research
• Rafal Wiewiora, MSKCC
• Bing Xie, Illinois Institute of Technology
• Huafeng Xu, D. E. Shaw Research
• Xin Yan, Yale University
• Ellen Zhong, D. E. Shaw Research
• Sean Zhu, Bristol-Myers Squibb