Göttingen 2019

Description

The European Alchemical Free Energy Workshop was held on May 27-28, 2019. BioExcel, the leading European Centre of Excellence for Computational Biomolecular Research, organized the event with a high-level lineup of speakers from both academia and industry. The current event is hosted and organized by the Max Planck Institute for Biophysical Chemistry in Göttingen.

Over the two days, the event gathered free energy calculation practitioners and method developers, both from academia and industry. In the spirit of similar previous workshops, we are interested in hearing about use cases, pitfalls and their solutions, as well as challenges and possible paths forward for improvement.

Organization Committee

Keynote Speaker: William L. Jorgensen

Institution: Professor, Department of Chemistry, Yale University, New Haven, USA
Title: “FEP for Drug Design Including Computation of Absolute Free Energies of Binding”

Schedule

May 27th, 2019 (Day 1)

Time (CEST)	Speaker	Title
9:00	Bert L. de Groot	Welcome and Opening Remarks
Session Chair: Matteo Aldeghi
9:15	John D. Chodera	Adaptive Free Energy Calculations and Free-Energy Guided Design
9:45	Antonia Mey	Reproducible Free Energy Workflows with BioSimSpace
10:15	Niels Hansen	Probing Different Aspects of Stability for the Pin1-WW Domain
10:35	BREAK
11:00	Herman van Vlijmen	Prediction of Activity Cliffs Using FEP+ and Gromacs FEP
11:30	Peter V. Coveney	Performance of Alchemical Relative Free Energy Calculations With and Without Replica-Exchange
12:00	Willem Jespers	QligFEP: An Automated Workflow for Small Molecule Free Energy Calculations in Q
12:20	POSTERS/LUNCH
Session Chair: John D. Chodera
2:00	Clara Christ	From Seven Million to Four - Identifying Novel Covalent Binders for KRASG12C
2:30	Philip W. Fowler	Predicting Antimicrobial Resistance: The Role of Computational Modelling in Translating Genetics into Clinical Microbiology
3:00	Vytautas Gapsys	Large Scale pmx/Gromacs Based Non-Equilibrium Free Energy Calculations
3:20	BREAK
3:50	David L. Mobley	Improving the Accuracy of Binding Free Energy Calculations via Enhanced Binding Mode Sampling and Better Force Fields
4:20	Christina Schindler	Free Energy Calculations in Active Drug Discovery Projects: Use Cases and Challenges
4:40	William L. Jorgensen	FEP for Drug Design Including Computation of Absolute Free Energies of Binding
5:25	DISCUSSION

May 28th, 2019 (Day 2)

Time (CEST)	Speaker	Title
Session Chair: Vytautas Gapsys
9:00	Chris Oostenbrink	Applications and Advances in the One-Step Perturbation Approach
9:30	Daniel Seeliger	Fragment Binding Pose Predictions Using Unbiased Simulations and Markov-State-Models
10:00	Zoe Cournia	Using Free Energy Perturbation Calculations to Predict Relative Binding Affinities in Drug Design
10:30	BREAK
10:50	Jonathan W. Essex	The Role of Water in Mediating Biomolecular Binding: From Water Locations to Their Impact on Binding Affinity
11:20	Thomas Steinbrecher	In Silico Lead Optimization via Rapid Exploration of Synthetically Tractable Chemical Space with Combined Free Energy and Machine Learning Approaches
11:50	Andrea Rizzi	The SAMPL6 SAMPLing Challenge: Assessing the Reliability and Efficiency of Binding Free Energy Calculations
12:10	POSTERS/LUNCH
Session Chair: Bert L. de Groot
1:40	Philip C. Biggin	ABFE, Water and Chemists: A Useful Combination?
2:10	Zara Sands	Free Energy Perturbation Calculations: Going Beyond SAR Analysis?
2:40	Gregory A. Ross	Enhancing Relative Protein-Ligand Binding Free Energy Calculations With Grand Canonical Monte Carlo Simulations of Water Molecules
3:00	BREAK
3:30	Albert Pan	Using Long-Timescale Molecular Dynamics Simulations to Benchmark Enhanced Sampling Methods
4:00	Philip Kim	Integrated Design of Novel Biologics
4:20	Gerhard König	Free Energy Calculation Using a Reference State: Replica-Exchange Enveloping Distribution Sampling (RE-EDS)
4:50	Bert L. de Groot	Closing Remarks

Poster Session

May 28th, 2019 (Day 2)

Time (CEST)	Speaker	Title
Session Chair: Vytautas Gapsys
9:00	Chris Oostenbrink	Applications and Advances in the One-Step Perturbation Approach
9:30	Daniel Seeliger	Fragment Binding Pose Predictions Using Unbiased Simulations and Markov-State-Models
10:00	Zoe Cournia	Using Free Energy Perturbation Calculations to Predict Relative Binding Affinities in Drug Design
10:30	RREAK
10:50	Jonathan W. Essex	The Role of Water in Mediating Biomolecular Binding: From Water Locations to Their Impact on Binding Affinity
11:20	Thomas Steinbrecher	In Silico Lead Optimization via Rapid Exploration of Synthetically Tractable Chemical Space with Combined Free Energy and Machine Learning Approaches
11:50	Andrea Rizzi	The SAMPL6 SAMPLing Challenge: Assessing the Reliability and Efficiency of Binding Free Energy Calculations
12:10	POSTERS/LUNCH
Session Chair: Bert L. de Groot
1:40	Philip C. Biggin	ABFE, Water and Chemists: A Useful Combination?
2:10	Zara Sands	Free Energy Perturbation Calculations: Going Beyond SAR Analysis?
2:40	Gregory A. Ross	Enhancing Relative Protein-Ligand Binding Free Energy Calculations With Grand Canonical Monte Carlo Simulations of Water Molecules
3:00	RREAK
3:30	Albert Pan	Using Long-Timescale Molecular Dynamics Simulations to Benchmark Enhanced Sampling Methods
4:00	Philip Kim	Integrated Design of Novel Biologics
4:20	Gerhard König	Free Energy Calculation Using a Reference State: Replica-Exchange Enveloping Distribution Sampling (RE-EDS)
4:50	Bert L. de Groot	Closing Remarks

Poster Session

Presenter	Affiliation	Title
Maximilian Kuhn	Cresset and University of Edinburgh	Developing a Robust Method for Automated Assessment of Binding Affinity via Free Energy Perturbation
Martin Werner	Max Planck Institute for Biophysical Chemistry	Analysis of Thermodynamic Coupling via Alchemical Free Energy Calculations
Gloria Angelica Sandoval-Pérez	University of los Andes	Unveiling the molecular mechanism underlying a bleeding disorder by using free energy calculations
Tim Hempel	Free University of Berlin	Calcium sensor proteins: Can we model ion binding free energies as a function of metastable Markov states?
Yaozong Li	University of Zurich	Repulsive soft-core potentials for efficient alchemical free energy calculations
Joe Bluck	University of Oxford	Towards using absolute binding free energy calculations in the early stages of ligand development
Elena Lilkova	Institute of Information and Communication Technologies	Mutation Free Energies of Human Interferon-Gamma Analogues
Johannes Dietschreit	LMU Munich	Insights into Chemistry through the Computation of Free Energy Hot-Spots
Joan Francesc Gilabert	Barcelona Supercomputing Center	Estimation of absolute and relative binding free energies with PELE
Nicolas Künzel	University of Saarland	How Phosphorylation Affects the Binding of C-terminal Peptides to PDZ Domains
Gabor Nagy	Max Planck Institute for Biophysical Chemistry	14-3-3 Protein Peptide-binding Pathways from Distance Field Replica Exchange
Christian Wennberg	ERCO Pharma AB	Skin permeability modeling using the Martini force field
Cecilia Chavez Garcia	The University of Western Ontario	Funnel metadynamics on the Kelch domain of Keap1
Vinaya Kumar Golla	Jacobs University Bremen	Estimation of free energy surfaces for substrate translocation – Metadynamics versus umbrella sampling
Ksenia Korshunova	Jülich Research Centre	Combining Force Field-based Hybrid Schemes for Grand-canonical Simulations of Low-resolution Models of GPCRs
Israel Cabeza de Vaca Lopez	Yale University	A free energy convergence study for proteins and molecules in solutions through Monte Carlo methods
Charles Robert	CNRS	Identifying determinants of RNA affinity and specificity in nuclear proteins regulating organelle gene expression
Ruo-Xu Gu	Max Planck Institute for Biophysical Chemistry	Lipid-Protein Interactions in Potassium Channel Permeation and Gating
Lucia Fusani	GSK and University of Strathclyde	A metadynamics protocol to predict the correct ligand binding pose
Simon Boothroyd	MSKCC	An automated, efficient, and scalable framework for the benchmarking of molecular force fields, and estimation of physical properties from molecular simulation
Daniel Kuhn	Merck	The Open Force Field Consortium - Open Force Fields in Industrial Pharmaceutical R&D
Dimitrios Stamatis	University of Athens	Alchemical Free Energy Calculations of Aminoadamantanes Bound to the Closed State of Influenza A/M2TM
Paul Czodrowski	TU Dortmund University	Future plans for the Statistical Assessment of the Modeling of Proteins and Ligands project
Ravi Tripathi	Ruhr University Bochum	Exploring the complex free-energy landscape of hGBP1 GTPase and its mutants utilizing ab initio QM/MM metadynamics simulations
Jan Walther Perthold	BOKU Vienna	Automated Free Energy Calculation for Drug Design: Accelerated Enveloping Distribution Sampling
Martin Reinhardt	Max Planck Institute for Biophysical Chemistry	Determining Free Energy Differences Through Variational Morphing
Ying-Chih Chiang	University of Southampton	Relaxation-Augmented Free Energy Perturbation
Mazen Ahmad	Max Planck Institute for Informatics	Relative Principal Components Analysis
Magnus Lundborg	ERCO Pharma	Calculating permeability through skin
Zhiyi Wu	Univeristy of Oxford	Proton-control of transitions in an amino-acid transporter
Christoph Öhlknecht	BOKU Vienna	Net Charge Changes in the Calculation of Protein-Ligand Binding Free Energies via Classical Atomistic MD Simulation
Jigneshkumar Dahyabhai Prajapati	Jacobs University Bremen	Minimum free energy pathways of ciprofloxacin and enrofloxacin across a bacterial pore
Ennys Gheyouche	University of Nantes	Exploration Of The Activation Mechanism Of Small GTPase RhoA
Clemens Rauer	Max Planck Institute for Polymer Research	Machine Learning of Hydration Free Energies
Bernadette Mohr	Max Planck Institute for Polymer Research	Optimization of drug-membrane selectivity from free-energy calculations
Alexander Kötter	University of Münster	Standard binding free energies of SIM SUMO complexes
Narendra Kumar	Ruhr University Bochum	Molecular Dynamics Study of Pressure-induced Effects on the Self-cleavage Catalysis Reaction of Hairpin Ribozyme
Steffen Wolf	University of Freiburg	Dissipation-corrected targeted molecular dynamics for the calculation of free energies and friction factors from non-equilibrium simulations of protein-ligand unbinding
Pierre Matricon	Uppsala University	Structure-Based Ligand Design by Targeting an Ordered Water: Interact, Displace, or Replace?
Martin Carballo-Pacheco	University of Edinburgh	Building fitness landscapes for antimicrobial resistance from free energy calculations
Efpraxia Tzortzini and Margarita Stampelou	University of Athens	Development of binding free energy computational models for GPCRs using the MM-PBSA method
Angelo Spinello	SISSA	Exploiting Enhanced Sampling Methods to Design Novel Allosteric Inhibitors of the Aromatase Enzyme
Tanadet Pipatpolkai	University of Oxford	PIP2 Modulation of KATP Channel and Disease
David F. Hahn	ETH Zurich	Multiple-replica λ-dynamics for the Calculation of Alchemical Free-Energies: The Conveyor Belt Thermodynamic Integration (CBTI) scheme
Emmi Pohjolainen	University of Jyväskylä	Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations
Willem Jespers	Uppsala University	Ligand and Sidechain Mutations by FEP Simulations: Two Sides of The Same Coin
Dimitris Ntekoumes	Biomedical Research Foundation of the Academy of Athens	Free Energy Calculations as a Tool for Lead Optimization in Drug Discovery