Pre-Exascale Computing of Protein-Ligand Binding Free Energies with Open Source Software for Drug Design

被引：39

作者：

Gapsys, Vytautas ^{[4
]}

Hahn, David F. ^{[1
]}

Tresadern, Gary ^{[1
]}

Mobley, David L. ^{[2
]}

Rampp, Markus ^{[3
]}

de Groot, Bert L. ^{[4
]}

机构：

[1] Janssen Pharmaceut NV, Janssen Res & Dev, Computat Chem, B-2340 Beerse, Belgium

[2] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA

[3] Max Planck Comp & Data Facil, D-85748 Garching, Germany

[4] Max Planck Inst Biophys Chem, Computat Biomol Dynam Grp, D-37077 Gottingen, Germany

来源：

JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2022年 / 62卷 / 05期

基金：

欧盟地平线“2020”;

关键词：

FORCE-FIELDS; ACCURATE; PREDICTION;

D O I：

10.1021/acs.jcim.1c01445

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nowadays, drug design projects benefit from highly accurate protein-ligand binding free energy predictions based on molecular dynamics simulations. While such calculations have been computationally expensive in the past, we now demonstrate that workflows built on open source software packages can efficiently leverage pre-exascale computing resources to screen hundreds of compounds in a matter of days. We report our results of free energy calculations on a large set of pharmaceutically relevant targets assembled to reflect industrial drug discovery projects.

引用

页码：1172 / 1177

页数：6

共 29 条

[21] Development and Benchmarking of Open Force Field v1.0.0-the Parsley Small-Molecule Force Field [J].

Qiu, Yudong ;

Smith, Daniel G. A. ;

Boothroyd, Simon ;

Jang, Hyesu ;

Hahn, David F. ;

Wagner, Jeffrey ;

Bannan, Caitlin C. ;

Gokey, Trevor ;

Lim, Victoria T. ;

Stern, Chaya D. ;

Rizzi, Andrea ;

Tjanaka, Bryon ;

Tresadern, Gary ;

Lucas, Xavier ;

Shirts, Michael R. ;

Gilson, Michael K. ;

Chodera, John D. ;

Bayly, Christopher, I ;

Mobley, David L. ;

Wang, Lee-Ping .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2021, 17 (10) :6262-6280

[22] Automated, Accurate, and Scalable Relative Protein-Ligand Binding Free-Energy Calculations Using Lambda Dynamics [J].

Raman, E. Prabhu ;

Paul, Thomas J. ;

Hayes, Ryan L. ;

Brooks, Charles L., III .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2020, 16 (12) :7895-7914

[23] Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects [J].

Schindler, Christina E. M. ;

Baumann, Hannah ;

Blum, Andreas ;

Boese, Dietrich ;

Buchstaller, Hans-Peter ;

Burgdorf, Lars ;

Cappel, Daniel ;

Chekler, Eugene ;

Czodrowski, Paul ;

Dorsch, Dieter ;

Eguida, Merveille K., I ;

Follows, Bruce ;

Fuchss, Thomas ;

Graedler, Ulrich ;

Gunera, Jakub ;

Johnson, Theresa ;

Lebrun, Catherine Jorand ;

Karra, Srinivasa ;

Klein, Markus ;

Knehans, Tim ;

Koetzner, Lisa ;

Krier, Mireille ;

Leiendecker, Matthias ;

Leuthner, Birgitta ;

Li, Liwei ;

Mochalkin, Igor ;

Musil, Djordje ;

Neagu, Constantin ;

Rippmann, Friedrich ;

Schiemann, Kai ;

Schulz, Robert ;

Steinbrecher, Thomas ;

Tanzer, Eva-Maria ;

Lopez, Andrea Unzue ;

Follis, Ariele Viacava ;

Wegener, Ansgar ;

Kuhn, Daniel .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2020, 60 (11) :5457-5474

[24] Using AMBER18 for Relative Free Energy Calculations [J].

Song, Lin Frank ;

Lee, Tai-Sung ;

Zhu, Chun ;

York, Darrin M. ;

Merz, Kenneth M., Jr. .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2019, 59 (07) :3128-3135

[25]

Wagner J., 2019, Zenodo

[26] Development and testing of a general amber force field [J].

Wang, JM ;

Wolf, RM ;

Caldwell, JW ;

Kollman, PA ;

Case, DA .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2004, 25 (09) :1157-1174

[27] Automatic atom type and bond type perception in molecular mechanical calculations [J].

Wang, Junmei ;

Wang, Wei ;

Kollman, Peter A. ;

Case, David A. .

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2006, 25 (02) :247-260

[28] Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field [J].

Wang, Lingle ;

Wu, Yujie ;

Deng, Yuqing ;

Kim, Byungchan ;

Pierce, Levi ;

Krilov, Goran ;

Lupyan, Dmitry ;

Robinson, Shaughnessy ;

Dahlgren, Markus K. ;

Greenwood, Jeremy ;

Romero, Donna L. ;

Masse, Craig ;

Knight, Jennifer L. ;

Steinbrecher, Thomas ;

Beuming, Thijs ;

Damm, Wolfgang ;

Harder, Ed ;

Sherman, Woody ;

Brewer, Mark ;

Wester, Ron ;

Murcko, Mark ;

Frye, Leah ;

Farid, Ramy ;

Lin, Teng ;

Mobley, David L. ;

Jorgensen, William L. ;

Berne, Bruce J. ;

Friesner, Richard A. ;

Abel, Robert .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2015, 137 (07) :2695-2703

[29] MATCH: An Atom-Typing Toolset for Molecular Mechanics Force Fields [J].

Yesselman, Joseph D. ;

Price, Daniel J. ;

Knight, Jennifer L. ;

Brooks, Charles L., III .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2012, 33 (02) :189-202

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