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Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects
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    Computational Chemistry

    Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects
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    • Christina E. M. Schindler*
      Christina E. M. Schindler
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      *Email: [email protected]
    • Hannah Baumann
      Hannah Baumann
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Andreas Blum
      Andreas Blum
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      More by Andreas Blum
    • Dietrich Böse
      Dietrich Böse
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Hans-Peter Buchstaller
      Hans-Peter Buchstaller
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Lars Burgdorf
      Lars Burgdorf
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Daniel Cappel
      Daniel Cappel
      Schrödinger GmbH, Q7 23, 68161 Mannheim, Germany
    • Eugene Chekler
      Eugene Chekler
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Paul Czodrowski
      Paul Czodrowski
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Dieter Dorsch
      Dieter Dorsch
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Merveille K. I. Eguida
      Merveille K. I. Eguida
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Bruce Follows
      Bruce Follows
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Thomas Fuchß
      Thomas Fuchß
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Ulrich Grädler
      Ulrich Grädler
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Jakub Gunera
      Jakub Gunera
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      More by Jakub Gunera
    • Theresa Johnson
      Theresa Johnson
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Catherine Jorand Lebrun
      Catherine Jorand Lebrun
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Srinivasa Karra
      Srinivasa Karra
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Markus Klein
      Markus Klein
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      More by Markus Klein
    • Tim Knehans
      Tim Knehans
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      More by Tim Knehans
    • Lisa Koetzner
      Lisa Koetzner
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Mireille Krier
      Mireille Krier
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Matthias Leiendecker
      Matthias Leiendecker
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Birgitta Leuthner
      Birgitta Leuthner
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Liwei Li
      Liwei Li
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
      More by Liwei Li
    • Igor Mochalkin
      Igor Mochalkin
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Djordje Musil
      Djordje Musil
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Constantin Neagu
      Constantin Neagu
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Friedrich Rippmann
      Friedrich Rippmann
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Kai Schiemann
      Kai Schiemann
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Robert Schulz
      Robert Schulz
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany
    • Thomas Steinbrecher
      Thomas Steinbrecher
      Schrödinger GmbH, Q7 23, 68161 Mannheim, Germany
    • Eva-Maria Tanzer
      Eva-Maria Tanzer
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Andrea Unzue Lopez
      Andrea Unzue Lopez
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Ariele Viacava Follis
      Ariele Viacava Follis
      EMD Serono Research and Development Institute Inc., 45A Middlesex Turnpike, Billerica, Massachusetts 01821, United States
    • Ansgar Wegener
      Ansgar Wegener
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
    • Daniel Kuhn*
      Daniel Kuhn
      Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
      *Email: [email protected]
      More by Daniel Kuhn
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    Journal of Chemical Information and Modeling

    Cite this: J. Chem. Inf. Model. 2020, 60, 11, 5457–5474
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    https://doi.org/10.1021/acs.jcim.0c00900
    Published August 19, 2020
    Copyright © 2020 American Chemical Society

    Abstract

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    Accurate ranking of compounds with regards to their binding affinity to a protein using computational methods is of great interest to pharmaceutical research. Physics-based free energy calculations are regarded as the most rigorous way to estimate binding affinity. In recent years, many retrospective studies carried out both in academia and industry have demonstrated its potential. Here, we present the results of large-scale prospective application of the FEP+ method in active drug discovery projects in an industry setting at Merck KGaA, Darmstadt, Germany. We compare these prospective data to results obtained on a new diverse, public benchmark of eight pharmaceutically relevant targets. Our results offer insights into the challenges faced when using free energy calculations in real-life drug discovery projects and identify limitations that could be tackled by future method development. The new public data set we provide to the community can support further method development and comparative benchmarking of free energy calculations.

    Copyright © 2020 American Chemical Society

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jcim.0c00900.

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    51. Wenlang Liu, Zhenhao Liu, Hao Liu, Lance M. Westerhoff, Zheng Zheng. Free Energy Calculations Using the Movable Type Method with Molecular Dynamics Driven Protein–Ligand Sampling. Journal of Chemical Information and Modeling 2022, 62 (22) , 5645-5665. https://doi.org/10.1021/acs.jcim.2c00278
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    53. Yuriy Khalak, Gary Tresadern, David F. Hahn, Bert L. de Groot, Vytautas Gapsys. Chemical Space Exploration with Active Learning and Alchemical Free Energies. Journal of Chemical Theory and Computation 2022, 18 (10) , 6259-6270. https://doi.org/10.1021/acs.jctc.2c00752
    54. Yuan Hu, Ingo Muegge. In Silico Positional Analogue Scanning with Amber GPU-TI. Journal of Chemical Information and Modeling 2022, 62 (18) , 4448-4459. https://doi.org/10.1021/acs.jcim.2c00860
    55. Asuka A. Orr, Suliman Sharif, Junmei Wang, Alexander D. MacKerell, Jr.. Preserving the Integrity of Empirical Force Fields. Journal of Chemical Information and Modeling 2022, 62 (16) , 3825-3831. https://doi.org/10.1021/acs.jcim.2c00615
    56. Maria Antonietta La Serra, Pietro Vidossich, Isabella Acquistapace, Anand K. Ganesan, Marco De Vivo. Alchemical Free Energy Calculations to Investigate Protein–Protein Interactions: the Case of the CDC42/PAK1 Complex. Journal of Chemical Information and Modeling 2022, 62 (12) , 3023-3033. https://doi.org/10.1021/acs.jcim.2c00348
    57. Piero Procacci. Relative Binding Free Energy between Chemically Distant Compounds Using a Bidirectional Nonequilibrium Approach. Journal of Chemical Theory and Computation 2022, 18 (6) , 4014-4026. https://doi.org/10.1021/acs.jctc.2c00295
    58. Lorena Zara, Francesca Moraca, Jacqueline E. Van Muijlwijk-Koezen, Barbara Zarzycka, Robert Abel, Iwan J. P. de Esch. Exploring the Activity Profile of TbrPDEB1 and hPDE4 Inhibitors Using Free Energy Perturbation. ACS Medicinal Chemistry Letters 2022, 13 (6) , 904-910. https://doi.org/10.1021/acsmedchemlett.1c00690
    59. Shunzhou Wan, Agastya P. Bhati, David W. Wright, Ian D. Wall, Alan P. Graves, Darren Green, Peter V. Coveney. Ensemble Simulations and Experimental Free Energy Distributions: Evaluation and Characterization of Isoxazole Amides as SMYD3 Inhibitors. Journal of Chemical Information and Modeling 2022, 62 (10) , 2561-2570. https://doi.org/10.1021/acs.jcim.2c00255
    60. Andrew T. McNutt, David Ryan Koes. Improving ΔΔG Predictions with a Multitask Convolutional Siamese Network. Journal of Chemical Information and Modeling 2022, 62 (8) , 1819-1829. https://doi.org/10.1021/acs.jcim.1c01497
    61. Ryan L. Hayes, Jonah Z. Vilseck, Charles L. Brooks III. Addressing Intersite Coupling Unlocks Large Combinatorial Chemical Spaces for Alchemical Free Energy Methods. Journal of Chemical Theory and Computation 2022, 18 (4) , 2114-2123. https://doi.org/10.1021/acs.jctc.1c00948
    62. Carsten Kutzner, Christian Kniep, Austin Cherian, Ludvig Nordstrom, Helmut Grubmüller, Bert L. de Groot, Vytautas Gapsys. GROMACS in the Cloud: A Global Supercomputer to Speed Up Alchemical Drug Design. Journal of Chemical Information and Modeling 2022, 62 (7) , 1691-1711. https://doi.org/10.1021/acs.jcim.2c00044
    63. Jonah Z. Vilseck, Luis F. Cervantes, Ryan L. Hayes, Charles L. Brooks III. Optimizing Multisite λ-Dynamics Throughput with Charge Renormalization. Journal of Chemical Information and Modeling 2022, 62 (6) , 1479-1488. https://doi.org/10.1021/acs.jcim.2c00047
    64. Vytautas Gapsys, David F. Hahn, Gary Tresadern, David L. Mobley, Markus Rampp, Bert L. de Groot. Pre-Exascale Computing of Protein–Ligand Binding Free Energies with Open Source Software for Drug Design. Journal of Chemical Information and Modeling 2022, 62 (5) , 1172-1177. https://doi.org/10.1021/acs.jcim.1c01445
    65. Yunhui Ge, David C. Wych, Marley L. Samways, Michael E. Wall, Jonathan W. Essex, David L. Mobley. Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques. Journal of Chemical Theory and Computation 2022, 18 (3) , 1359-1381. https://doi.org/10.1021/acs.jctc.1c00590
    66. Pengfei Li, Zhijie Li, Yu Wang, Huaixia Dou, Brian K. Radak, Bryce K. Allen, Woody Sherman, Huafeng Xu. Precise Binding Free Energy Calculations for Multiple Molecules Using an Optimal Measurement Network of Pairwise Differences. Journal of Chemical Theory and Computation 2022, 18 (2) , 650-663. https://doi.org/10.1021/acs.jctc.1c00703
    67. Miriam Jäger, Thorsten Koslowski, Steffen Wolf. Predicting Ion Channel Conductance via Dissipation-Corrected Targeted Molecular Dynamics and Langevin Equation Simulations. Journal of Chemical Theory and Computation 2022, 18 (1) , 494-502. https://doi.org/10.1021/acs.jctc.1c00426
    68. Ann E. Cleves, Stephen R. Johnson, Ajay N. Jain. Synergy and Complementarity between Focused Machine Learning and Physics-Based Simulation in Affinity Prediction. Journal of Chemical Information and Modeling 2021, 61 (12) , 5948-5966. https://doi.org/10.1021/acs.jcim.1c01382
    69. Zoe Cournia Christophe Chipot Benoît Roux Darrin M. York Woody Sherman . Free Energy Methods in Drug Discovery—Introduction. , 1-38. https://doi.org/10.1021/bk-2021-1397.ch001
    70. Katharina Meier Joseph P. Bluck Clara D. Christ . Use of Free Energy Methods in the Drug Discovery Industry. , 39-66. https://doi.org/10.1021/bk-2021-1397.ch002
    71. Tai-Sung Lee Hsu-Chun Tsai Abir Ganguly Timothy J. Giese Darrin M. York . Robust, Efficient and Automated Methods for Accurate Prediction of Protein-Ligand Binding Affinities in AMBER Drug Discovery Boost. , 161-204. https://doi.org/10.1021/bk-2021-1397.ch007
    72. Ryan L. Hayes, Joshua Buckner, Charles L. Brooks, III. BLaDE: A Basic Lambda Dynamics Engine for GPU-Accelerated Molecular Dynamics Free Energy Calculations. Journal of Chemical Theory and Computation 2021, 17 (11) , 6799-6807. https://doi.org/10.1021/acs.jctc.1c00833
    73. Yudong Qiu, Daniel G. A. Smith, Simon Boothroyd, Hyesu Jang, David F. Hahn, Jeffrey Wagner, Caitlin C. Bannan, Trevor Gokey, Victoria T. Lim, Chaya D. Stern, Andrea Rizzi, Bryon Tjanaka, Gary Tresadern, Xavier Lucas, Michael R. Shirts, Michael K. Gilson, John D. Chodera, Christopher I. Bayly, David L. Mobley, Lee-Ping Wang. Development and Benchmarking of Open Force Field v1.0.0—the Parsley Small-Molecule Force Field. Journal of Chemical Theory and Computation 2021, 17 (10) , 6262-6280. https://doi.org/10.1021/acs.jctc.1c00571
    74. Stamatia Zavitsanou, Alexandros Tsengenes, Michail Papadourakis, Giorgio Amendola, Alexios Chatzigoulas, Dimitris Dellis, Sandro Cosconati, Zoe Cournia. FEPrepare: A Web-Based Tool for Automating the Setup of Relative Binding Free Energy Calculations. Journal of Chemical Information and Modeling 2021, 61 (9) , 4131-4138. https://doi.org/10.1021/acs.jcim.1c00215
    75. Jonah Z. Vilseck, Xinqiang Ding, Ryan L. Hayes, Charles L. Brooks III. Generalizing the Discrete Gibbs Sampler-Based λ-Dynamics Approach for Multisite Sampling of Many Ligands. Journal of Chemical Theory and Computation 2021, 17 (7) , 3895-3907. https://doi.org/10.1021/acs.jctc.1c00176
    76. Luan Carvalho Martins, Elio A. Cino, Rafaela Salgado Ferreira. PyAutoFEP: An Automated Free Energy Perturbation Workflow for GROMACS Integrating Enhanced Sampling Methods. Journal of Chemical Theory and Computation 2021, 17 (7) , 4262-4273. https://doi.org/10.1021/acs.jctc.1c00194
    77. Chao Lu, Chuanjie Wu, Delaram Ghoreishi, Wei Chen, Lingle Wang, Wolfgang Damm, Gregory A. Ross, Markus K. Dahlgren, Ellery Russell, Christopher D. Von Bargen, Robert Abel, Richard A. Friesner, Edward D. Harder. OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space. Journal of Chemical Theory and Computation 2021, 17 (7) , 4291-4300. https://doi.org/10.1021/acs.jctc.1c00302
    78. Junjie Zou, Zhipeng Li, Shuai Liu, Chunwang Peng, Dong Fang, Xiao Wan, Zhixiong Lin, Tai-Sung Lee, Daniel P. Raleigh, Mingjun Yang, Carlos Simmerling. Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies. Journal of Chemical Theory and Computation 2021, 17 (6) , 3710-3726. https://doi.org/10.1021/acs.jctc.1c00214
    79. Lauren Nelson, Sofia Bariami, Chris Ringrose, Joshua T. Horton, Vadiraj Kurdekar, Antonia S. J. S. Mey, Julien Michel, Daniel J. Cole. Implementation of the QUBE Force Field in SOMD for High-Throughput Alchemical Free-Energy Calculations. Journal of Chemical Information and Modeling 2021, 61 (5) , 2124-2130. https://doi.org/10.1021/acs.jcim.1c00328
    80. Hannah M. Baumann, Vytautas Gapsys, Bert L. de Groot, David L. Mobley. Challenges Encountered Applying Equilibrium and Nonequilibrium Binding Free Energy Calculations. The Journal of Physical Chemistry B 2021, 125 (17) , 4241-4261. https://doi.org/10.1021/acs.jpcb.0c10263
    81. Edward B. Miller, Robert B. Murphy, Daniel Sindhikara, Kenneth W. Borrelli, Matthew J. Grisewood, Fabio Ranalli, Steven L. Dixon, Steven Jerome, Nicholas A. Boyles, Tyler Day, Phani Ghanakota, Sayan Mondal, Salma B. Rafi, Dawn M. Troast, Robert Abel, Richard A. Friesner. Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein–Ligand Binding. Journal of Chemical Theory and Computation 2021, 17 (4) , 2630-2639. https://doi.org/10.1021/acs.jctc.1c00136
    82. Samuel C. Gill, David L. Mobley. Reversibly Sampling Conformations and Binding Modes Using Molecular Darting. Journal of Chemical Theory and Computation 2021, 17 (1) , 302-314. https://doi.org/10.1021/acs.jctc.0c00752
    83. E. Prabhu Raman, Thomas J. Paul, Ryan L. Hayes, Charles L. Brooks, III. Automated, Accurate, and Scalable Relative Protein–Ligand Binding Free-Energy Calculations Using Lambda Dynamics. Journal of Chemical Theory and Computation 2020, 16 (12) , 7895-7914. https://doi.org/10.1021/acs.jctc.0c00830
    84. Lin Frank Song, Kenneth M. Merz, Jr.. Evolution of Alchemical Free Energy Methods in Drug Discovery. Journal of Chemical Information and Modeling 2020, 60 (11) , 5308-5318. https://doi.org/10.1021/acs.jcim.0c00547
    85. Kira A. Armacost, Sereina Riniker, Zoe Cournia. Exploring Novel Directions in Free Energy Calculations. Journal of Chemical Information and Modeling 2020, 60 (11) , 5283-5286. https://doi.org/10.1021/acs.jcim.0c01266
    86. Gary Tresadern, Ingrid Velter, Andrés A. Trabanco, Frans Van den Keybus, Gregor J. Macdonald, Marijke V. F. Somers, Greet Vanhoof, Philip M. Leonard, Marieke B. A. C. Lamers, Yves E. M. Van Roosbroeck, Peter J. J. A. Buijnsters. [1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration. Journal of Medicinal Chemistry 2020, 63 (21) , 12887-12910. https://doi.org/10.1021/acs.jmedchem.0c01272
    87. , Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry van den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Pawel Gniewek, Sam Eckert, Saulo de Oliveira, Shabbir Suterwala, Srimukh Veccham Krishna PrasadPrasad, Stefani Shek, Stephanie Contreras, Stephanie Hare, Teresa Palazzo, Terrence E. O’Brien, Tessa Van Grack, Tiffany Williams, Ting-Rong Chern, Victor Kenyon, Andreia H. Lee, Andrew B. Cann, Bastiaan Bergman, Brandon M. Anderson, Bryan D. Cox, Jeffrey M. Warrington, Jon M. Sorenson, Joshua M. Goldenberg, Matthew A. Young, Nicholas DeHaan, Ryan P. Pemberton, Stefan Schroedl, Tigran M. Abramyan, Tushita Gupta, Venkatesh Mysore, Adam G. Presser, Adolfo A. Ferrando, Adriano D. Andricopulo, Agnidipta Ghosh, Aicha Gharbi Ayachi, Aisha Mushtaq, Ala M. Shaqra, Alan Kie Leong Toh, Alan V. Smrcka, Alberto Ciccia, Aldo Sena de Oliveira, Aleksandr Sverzhinsky, Alessandra Mara de Sousa, Alexander I. Agoulnik, Alexander Kushnir, Alexander N. Freiberg, Alexander V. Statsyuk, Alexandre R. Gingras, Alexei Degterev, Alexey Tomilov, Alice Vrielink, Alisa A. Garaeva, Amanda Bryant-Friedrich, Amedeo Caflisch, Amit K. Patel, Amith Vikram Rangarajan, An Matheeussen, Andrea Battistoni, Andrea Caporali, Andrea Chini, Andrea Ilari, Andrea Mattevi, Andrea Talbot Foote, Andrea Trabocchi, Andreas Stahl, Andrew B. Herr, Andrew Berti, Andrew Freywald, Andrew G. Reidenbach, Andrew Lam, Andrew R. Cuddihy, Andrew White, Angelo Taglialatela, Anil K. Ojha, Ann M. Cathcart, Anna A. L. Motyl, Anna Borowska, Anna D’Antuono, Anna K. H. Hirsch, Anna Maria Porcelli, Anna Minakova, Anna Montanaro, Anna Müller, Annarita Fiorillo, Anniina Virtanen, Anthony J. O’Donoghue, Antonio Del Rio Flores, Antonio E. Garmendia, Antonio Pineda-Lucena, Antonito T. Panganiban, Ariela Samantha, Arnab K. Chatterjee, Arthur L. Haas, Ashleigh S. Paparella, Ashley L. St. John, Ashutosh Prince, Assmaa ElSheikh, Athena Marie Apfel, Audrey Colomba, Austin O’Dea, Bakary N’tji Diallo, Beatriz Murta Rezende Moraes Ribeiro, Ben A. Bailey-Elkin, Benjamin L. Edelman, Benjamin Liou, Benjamin Perry, Benjamin Soon Kai Chua, Benjámin Kováts, Bernhard Englinger, Bijina Balakrishnan, Bin Gong, Bogos Agianian, Brandon Pressly, Brenda P. Medellin Salas, Brendan M. Duggan, Brian V. Geisbrecht, Brian W. Dymock, Brianna C. Morten, Bruce D. Hammock, Bruno Eduardo Fernandes Mota, Bryan C. Dickinson, Cameron Fraser, Camille Lempicki, Carl D. Novina, Carles Torner, Carlo Ballatore, Carlotta Bon, Carly J. Chapman, Carrie L. Partch, Catherine T. Chaton, Chang Huang, Chao-Yie Yang, Charlene M. Kahler, Charles Karan, Charles Keller, Chelsea L. Dieck, Chen Huimei, Chen Liu, Cheryl Peltier, Chinmay Kumar Mantri, Chinyere Maat Kemet, Christa E. Müller, Christian Weber, Christina M. Zeina, Christine S. Muli, Christophe Morisseau, Cigdem Alkan, Clara Reglero, Cody A. Loy, Cornelia M. Wilson, Courtney Myhr, Cristina Arrigoni, Cristina Paulino, César Santiago, Dahai Luo, Damon J. Tumes, Daniel A. Keedy, Daniel A. Lawrence, Daniel Chen, Danny Manor, Darci J. Trader, David A. Hildeman, David H. Drewry, David J. Dowling, David J. Hosfield, David M. Smith, David Moreira, David P. Siderovski, David Shum, David T. Krist, David W. H. Riches, Davide Maria Ferraris, Deborah H. Anderson, Deirdre R. Coombe, Derek S. Welsbie, Di Hu, Diana Ortiz, Dina Alramadhani, Dingqiang Zhang, Dipayan Chaudhuri, Dirk J. Slotboom, Donald R. Ronning, Donghan Lee, Dorian Dirksen, Douglas A. Shoue, Douglas William Zochodne, Durga Krishnamurthy, Dustin Duncan, Dylan M. Glubb, Edoardo Luigi Maria Gelardi, Edward C. Hsiao, Edward G. Lynn, Elany Barbosa Silva, Elena Aguilera, Elena Lenci, Elena Theres Abraham, Eleonora Lama, Eleonora Mameli, Elisa Leung, Ellie Giles, Emily M. Christensen, Emily R. Mason, Enrico Petretto, Ephraim F. Trakhtenberg, Eric J. Rubin, Erick Strauss, Erik W. Thompson, Erika Cione, Erika Mathes Lisabeth, Erkang Fan, Erna Geessien Kroon, Eunji Jo, Eva M. García-Cuesta, Evgenia Glukhov, Evripidis Gavathiotis, Fang Yu, Fei Xiang, Fenfei Leng, Feng Wang, Filippo Ingoglia, Focco van den Akker, Francesco Borriello, Franco J. Vizeacoumar, Frank Luh, Frederick S. Buckner, Frederick S. Vizeacoumar, Fredj Ben Bdira, Fredrik Svensson, G. Marcela Rodriguez, Gabriella Bognár, Gaia Lembo, Gang Zhang, Garrett Dempsey, Gary Eitzen, Gaétan Mayer, Geoffrey L. Greene, George A. Garcia, Gergely L. Lukacs, Gergely Prikler, Gian Carlo G. Parico, Gianni Colotti, Gilles De Keulenaer, Gino Cortopassi, Giovanni Roti, Giulia Girolimetti, Giuseppe Fiermonte, Giuseppe Gasparre, Giuseppe Leuzzi, Gopal Dahal, Gracjan Michlewski, Graeme L. Conn, Grant David Stuchbury, Gregory R. Bowman, Grzegorz Maria Popowicz, Guido Veit, Guilherme Eduardo de Souza, Gustav Akk, Guy Caljon, Guzmán Alvarez, Gwennan Rucinski, Gyeongeun Lee, Gökhan Cildir, Hai Li, Hairol E. Breton, Hamed Jafar-Nejad, Han Zhou, Hannah P. Moore, Hannah Tilford, Haynes Yuan, Heesung Shim, Heike Wulff, Heinrich Hoppe, Helena Chaytow, Heng-Keat Tam, Holly Van Remmen, Hongyang Xu, Hosana Maria Debonsi, Howard B. Lieberman, Hoyoung Jung, Hua-Ying Fan, Hui Feng, Hui Zhou, Hyeong Jun Kim, Iain R. Greig, Ileana Caliandro, Ileana Corvo, Imanol Arozarena, Imran N. Mungrue, Ingrid M. Verhamme, Insaf Ahmed Qureshi, Irina Lotsaris, Isin Cakir, J. Jefferson P. Perry, Jacek Kwiatkowski, Jacob Boorman, Jacob Ferreira, Jacob Fries, Jadel Müller Kratz, Jaden Miner, Jair L. Siqueira-Neto, James G. Granneman, James Ng, James Shorter, Jan Hendrik Voss, Jan M. Gebauer, Janelle Chuah, Jarrod J. Mousa, Jason T. Maynes, Jay D. Evans, Jeffrey Dickhout, Jeffrey P. MacKeigan, Jennifer N. Jossart, Jia Zhou, Jiabei Lin, Jiake Xu, Jianghai Wang, Jiaqi Zhu, Jiayu Liao, Jingyi Xu, Jinshi Zhao, Jiusheng Lin, Jiyoun Lee, Joana Reis, Joerg Stetefeld, John B. Bruning, John Burt Bruning, John G. Coles, John J. Tanner, John M. Pascal, Jonathan So, Jordan L. Pederick, Jose A. Costoya, Joseph B. Rayman, Joseph J. Maciag, Joshua Alexander Nasburg, Joshua J. Gruber, Joshua M. Finkelstein, Joshua Watkins, José Miguel Rodríguez-Frade, Juan Antonio Sanchez Arias, Juan José Lasarte, Julen Oyarzabal, Julian Milosavljevic, Julie Cools, Julien Lescar, Julijus Bogomolovas, Jun Wang, Jung-Min Kee, Jung-Min Kee, Junzhuo Liao, Jyothi C. Sistla, Jônatas Santos Abrahão, Kamakshi Sishtla, Karol R. Francisco, Kasper B. Hansen, Kathleen A. Molyneaux, Kathryn A. Cunningham, Katie R. Martin, Kavita Gadar, Kayode K. Ojo, Keith S. Wong, Kelly L. Wentworth, Kent Lai, Kevin A. Lobb, Kevin M. Hopkins, Keykavous Parang, Khaled Machaca, Kien Pham, Kim Ghilarducci, Kim S. Sugamori, Kirk James McManus, Kirsikka Musta, Kiterie M. E. Faller, Kiyo Nagamori, Konrad J. Mostert, Konstantin V. Korotkov, Koting Liu, Kristiana S. Smith, Kristopher Sarosiek, Kyle H. Rohde, Kyu Kwang Kim, Kyung Hyeon Lee, Lajos Pusztai, Lari Lehtiö, Larisa M. Haupt, Leah E. Cowen, Lee J. Byrne, Leila Su, Leon Wert-Lamas, Leonor Puchades-Carrasco, Lifeng Chen, Linda H. Malkas, Ling Zhuo, Lizbeth Hedstrom, Lizbeth Hedstrom, Loren D. Walensky, Lorenzo Antonelli, Luisa Iommarini, Luke Whitesell, Lía M. Randall, M. Dahmani Fathallah, Maira Harume Nagai, Mairi Louise Kilkenny, Manu Ben-Johny, Marc P. Lussier, Marc P. Windisch, Marco Lolicato, Marco Lucio Lolli, Margot Vleminckx, Maria Cristina Caroleo, Maria J. Macias, Marilia Valli, Marim M. Barghash, Mario Mellado, Mark A. Tye, Mark A. Wilson, Mark Hannink, Mark R. Ashton, Mark Vincent C.dela Cerna, Marta Giorgis, Martin K. Safo, Martin St. Maurice, Mary Ann McDowell, Marzia Pasquali, Masfique Mehedi, Mateus Sá Magalhães Serafim, Matthew B. Soellner, Matthew G. Alteen, Matthew M. Champion, Maxim Skorodinsky, Megan L. O’Mara, Mel Bedi, Menico Rizzi, Michael Levin, Michael Mowat, Michael R. Jackson, Mikell Paige, Minnatallah Al-Yozbaki, Miriam A. Giardini, Mirko M. Maksimainen, Monica De Luise, Muhammad Saddam Hussain, Myron Christodoulides, Natalia Stec, Natalia Zelinskaya, Natascha Van Pelt, Nathan M. Merrill, Nathanael Singh, Neeltje A. Kootstra, Neeraj Singh, Neha S. Gandhi, Nei-Li Chan, Nguyen Mai Trinh, Nicholas O. Schneider, Nick Matovic, Nicola Horstmann, Nicola Longo, Nikhil Bharambe, Nirvan Rouzbeh, Niusha Mahmoodi, Njabulo Joyfull Gumede, Noelle C. Anastasio, Noureddine Ben Khalaf, Obdulia Rabal, Olga Kandror, Olivier Escaffre, Olli Silvennoinen, Ozlem Tastan Bishop, Pablo Iglesias, Pablo Sobrado, Patrick Chuong, Patrick O’Connell, Pau Martin-Malpartida, Paul Mellor, Paul V. Fish, Paulo Otávio Lourenço Moreira, Pei Zhou, Pengda Liu, Pengda Liu, Pengpeng Wu, Percy Agogo-Mawuli, Peter L. Jones, Peter Ngoi, Peter Toogood, Philbert Ip, Philipp von Hundelshausen, Pil H. Lee, Rachael B. Rowswell-Turner, Rafael Balaña-Fouce, Rafael Eduardo Oliveira Rocha, Rafael V. C. Guido, Rafaela Salgado Ferreira, Rajendra K. Agrawal, Rajesh K. Harijan, Rajesh Ramachandran, Rajkumar Verma, Rakesh K. Singh, Rakesh Kumar Tiwari, Ralph Mazitschek, Rama K. Koppisetti, Remus T. Dame, Renée N. Douville, Richard C. Austin, Richard E. Taylor, Richard G. Moore, Richard H. Ebright, Richard M. Angell, Riqiang Yan, Rishabh Kejriwal, Robert A. Batey, Robert Blelloch, Robert J. Vandenberg, Robert J. Hickey, Robert J. Kelm, Robert J. Lake, Robert K. Bradley, Robert M. Blumenthal, Roberto Solano, Robin Matthias Gierse, Ronald E. Viola, Ronan R. McCarthy, Rosa Maria Reguera, Ruben Vazquez Uribe, Rubens Lima do Monte-Neto, Ruggiero Gorgoglione, Ryan T. Cullinane, Sachin Katyal, Sakib Hossain, Sameer Phadke, Samuel A. Shelburne, Sandra E. Geden, Sandra Johannsen, Sarah Wazir, Scott Legare, Scott M. Landfear, Senthil K. Radhakrishnan, Serena Ammendola, Sergei Dzhumaev, Seung-Yong Seo, Shan Li, Shan Zhou, Shaoyou Chu, Shefali Chauhan, Shinsaku Maruta, Shireen R. Ashkar, Show-Ling Shyng, Silvestro G. Conticello, Silvia Buroni, Silvia Garavaglia, Simon J. White, Siran Zhu, Sofiya Tsimbalyuk, Somaia Haque Chadni, Soo Young Byun, Soonju Park, Sophia Q. Xu, Sourav Banerjee, Stefan Zahler, Stefano Espinoza, Stefano Gustincich, Stefano Sainas, Stephanie L. Celano, Stephen J. Capuzzi, Stephen N. Waggoner, Steve Poirier, Steven H. Olson, Steven O. Marx, Steven R. Van Doren, Suryakala Sarilla, Susann M. Brady-Kalnay, Sydney Dallman, Syeda Maryam Azeem, Tadahisa Teramoto, Tamar Mehlman, Tarryn Swart, Tatjana Abaffy, Tatos Akopian, Teemu Haikarainen, Teresa Lozano Moreda, Tetsuro Ikegami, Thaiz Rodrigues Teixeira, Thilina D. Jayasinghe, Thomas H. Gillingwater, Thomas Kampourakis, Timothy I. Richardson, Timothy J. Herdendorf, Timothy J. Kotzé, Timothy R. O’Meara, Timothy W. Corson, Tobias Hermle, Tomisin Happy Ogunwa, Tong Lan, Tong Su, Toshihiro Banjo, Tracy A. O’Mara, Tristan Chou, Tsui-Fen Chou, Ulrich Baumann, Umesh R. Desai, Vaibhav P. Pai, Van Chi Thai, Vasudha Tandon, Versha Banerji, Victoria L. Robinson, Vignesh Gunasekharan, Vigneshwaran Namasivayam, Vincent F. M. Segers, Vincent Maranda, Vincenza Dolce, Vinícius Gonçalves Maltarollo, Viola Camilla Scoffone, Virgil A. Woods, Virginia Paola Ronchi, Vuong Van Hung Le, W. Brent Clayton, W. Todd Lowther, Walid A. Houry, Wei Li, Weiping Tang, Wenjun Zhang, Wesley C. Van Voorhis, William A. Donaldson, William C. Hahn, William G. Kerr, William H. Gerwick, William J. Bradshaw, Wuen Ee Foong, Xavier Blanchet, Xiaoyang Wu, Xin Lu, Xin Qi, Xin Xu, Xinfang Yu, Xingping Qin, Xingyou Wang, Xinrui Yuan, Xu Zhang, Yan Jessie Zhang, Yanmei Hu, Yasser Ali Aldhamen, Yicheng Chen, Yihe Li, Ying Sun, Yini Zhu, Yogesh K. Gupta, Yolanda Pérez-Pertejo, Yong Li, Young Tang, Yuan He, Yuk-Ching Tse-Dinh, Yulia A. Sidorova, Yun Yen, Yunlong Li, Zachary J. Frangos, Zara Chung, Zhengchen Su, Zhenghe Wang, Zhiguo Zhang, Zhongle Liu, Zintis Inde, Zoraima Artía, Abraham Heifets. AI is a viable alternative to high throughput screening: a 318-target study. Scientific Reports 2024, 14 (1) https://doi.org/10.1038/s41598-024-54655-z
    88. Kenneth Atz, Leandro Cotos, Clemens Isert, Maria Håkansson, Dorota Focht, Mattis Hilleke, David F. Nippa, Michael Iff, Jann Ledergerber, Carl C. G. Schiebroek, Valentina Romeo, Jan A. Hiss, Daniel Merk, Petra Schneider, Bernd Kuhn, Uwe Grether, Gisbert Schneider. Prospective de novo drug design with deep interactome learning. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-47613-w
    89. Haixin Wei, J. Andrew McCammon. Structure and dynamics in drug discovery. npj Drug Discovery 2024, 1 (1) https://doi.org/10.1038/s44386-024-00001-2
    90. Alexander C. Brueckner, Benjamin Shields, Palani Kirubakaran, Alexander Suponya, Manoranjan Panda, Shana L. Posy, Stephen Johnson, Sirish Kaushik Lakkaraju. MDFit: automated molecular simulations workflow enables high throughput assessment of ligands-protein dynamics. Journal of Computer-Aided Molecular Design 2024, 38 (1) https://doi.org/10.1007/s10822-024-00564-2
    91. Dayan Liu, Tao Song, Shudong Wang. MM-DRPNet: A Multimodal Dynamic Radial Partitioning Network for Enhanced Protein–Ligand Binding Affinity Prediction. Computational and Structural Biotechnology Journal 2024, https://doi.org/10.1016/j.csbj.2024.11.050
    92. Michael Iff, Kenneth Atz, Clemens Isert, Irene Pachon-Angona, Leandro Cotos, Mattis Hilleke, Jan A. Hiss, Gisbert Schneider. Combining de novo molecular design with semiempirical protein–ligand binding free energy calculation. RSC Advances 2024, 14 (50) , 37035-37044. https://doi.org/10.1039/D4RA05422A
    93. Vytautas Gapsys, Wojciech Kopec, Dirk Matthes, Bert L. de Groot. Biomolecular simulations at the exascale: From drug design to organelles and beyond. Current Opinion in Structural Biology 2024, 88 , 102887. https://doi.org/10.1016/j.sbi.2024.102887
    94. Hannah M. Baumann, David L. Mobley. Impact of protein conformations on binding free energy calculations in the beta‐secretase 1 system. Journal of Computational Chemistry 2024, 45 (23) , 2024-2033. https://doi.org/10.1002/jcc.27365
    95. Kenichiro Takaba, Anika J. Friedman, Chapin E. Cavender, Pavan Kumar Behara, Iván Pulido, Michael M. Henry, Hugo MacDermott-Opeskin, Christopher R. Iacovella, Arnav M. Nagle, Alexander Matthew Payne, Michael R. Shirts, David L. Mobley, John D. Chodera, Yuanqing Wang. Machine-learned molecular mechanics force fields from large-scale quantum chemical data. Chemical Science 2024, 15 (32) , 12861-12878. https://doi.org/10.1039/D4SC00690A
    96. Froze Jameel, Matthias Stein. Chemical accuracy for ligand-receptor binding Gibbs energies through multi-level SQM/QM calculations. Physical Chemistry Chemical Physics 2024, 26 (31) , 21197-21203. https://doi.org/10.1039/D4CP01529K
    97. Bin Feng, Zequn Liu, Nanlan Huang, Zhiping Xiao, Haomiao Zhang, Srbuhi Mirzoyan, Hanwen Xu, Jiaran Hao, Yinghui Xu, Ming Zhang, Sheng Wang. A bioactivity foundation model using pairwise meta-learning. Nature Machine Intelligence 2024, 6 (8) , 962-974. https://doi.org/10.1038/s42256-024-00876-w
    98. Shuoyan Tan, Xiaoqing Gong, Huanxiang Liu, Xiaojun Yao. Identification of novel LRRK2 inhibitors by structure-based virtual screening and alchemical free energy calculation. Physical Chemistry Chemical Physics 2024, 26 (29) , 19775-19786. https://doi.org/10.1039/D4CP01762E
    99. Kairi Furui, Masahito Ohue. Fastlomap: faster lead optimization mapper algorithm for large-scale relative free energy perturbation. The Journal of Supercomputing 2024, 80 (10) , 14417-14432. https://doi.org/10.1007/s11227-024-06006-y
    100. Simon Barnett, John D. Chodera. Neural Network Potentials for Enabling Advanced Small-Molecule Drug Discovery and Generative Design. GEN Biotechnology 2024, 3 (3) , 119-129. https://doi.org/10.1089/genbio.2024.0011
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    Journal of Chemical Information and Modeling

    Cite this: J. Chem. Inf. Model. 2020, 60, 11, 5457–5474
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    https://doi.org/10.1021/acs.jcim.0c00900
    Published August 19, 2020
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