Felice Lightstone

Contact information

Lawrence Livermore National Laboratory
7000 East Avenue, L-372
Livermore, CA 94550
email: lightstone1@llnl.gov
phone: 925 423 8657
fax: 925 423 0785

Education

Ph.D. in Chemistry, University of California, 1998
M.S. in Electrical Engineering, University of Illinois, 1991
B.S. in Honors Biology, University of Illinois, 1990
B.S. in Electrical Engineering, University of Illinois, 1989

Research

I am the Biochemical and Biophysical Systems Group leader in Biosciences and Biotechnology Division at Lawrence Livermore National Laboratory.  My research involves the use of electronic structure methods, atomistic modeling, and molecular dynamics simulations to predict and understand the interaction of small molecules with proteins.  My projects include design and development of small molecule therapeutics, elucidating enzymatic mechanisms, and design of biomimetics.

Recent publications

B. J. Bennion, M. A. Malfatti, N. A. Be, H. A. Enright, S. Hok, C. L. Cadieux, T. S. Carpenter, V. Lao, E.A. Kuhn, M.W. McNerney, F. C. Lightstone, T. H. Nguyen, and C.A. Valdez (2021) Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach, Scientific Reports 11, 15567.

E. Y. Lau, O. A. Negrete, W. F. D.Bennett, B. J. Bennion, M. Borucki, F. Bourguet, A. Epstein, M. Franco, B. Harmon, S. He, D. Jones, H. Kim, D. Kirshner, V. Lao, J. Lo, K. McLoughlin, R. Mosesso, D. K. Murugesh, E. A. Saada, B. Segelke, M. A. Stefan, G. A. Stevenson, M. W. Torres, D. R. Weilhammer, S. Wong, Y. Yang, A. Zemla, X. Zhang, F. Zhu, J. E. Allen, F. C. Lightstone (2021) Discovery of Small-molecule Inhibitors of SARS-CoV-2 Proteins Using a Computational and Experimental Pipeline, Frontiers in Molecular Biosciences, 8, 644.

S. A. Jacobs, T. Moon, K. McLoughlin, D. Jones, D. Hysom, D. H. Ahn, J. Gyllenhaal, P. Watson, F. C. Lightstone, J. E. Allen, I. Karlin, B. Van Essen (2021) Enabling Rapid COVID-19 Small Molecule Drug Design Through Scalable Deep Learning of Generative Models, International Journal of High Performance Computing Applications, In press.

H. Bhatia, T. Carpenter , H. Ingolfsson , G. Dharuman , P. Karande , S. Liu , T. Oppelstrup , C. Neale , F. Lightstone , B. Van Essen , J. Glosli , P.-T. Bremer (2021) Machine Learning Based Dynamic-Importance Sampling for Adaptive Multiscale Simulations, Nature Machine Intelligence, https://doi.org/10.1038/s42256-021-00327-w.

D. Jones, H. Kim, X. Zhang, A. Zemla, G. Stevenson, W. F. D. Bennett, D. Kirshner, S. E. Wong, F. C. Lightstone, and J. E. Allen (2021) Improved Protein–Ligand Binding Affinity Prediction with Structure-Based Deep Fusion Inference, J. Chem. Info. Model., 61, 4, 1583–1592.

F. Cheng, J. Zhao, Y. Wang, W. Lu, Z. Liu, Y. Zhou, W. Martin, R. Wang, J. Huang, T. Hao, H. Yue, J. Ma, Y. Hou, J. Castrillon, J. Fang, J. Lathia, R. A. Keri, F. C. Lightstone, E. M. Antman, R. Rabadan, D. E. Hill, C. Eng, M. Vidal, J. Loscalzo (2021) Comprehensive characterization of protein-protein interaction network perturbations by human disease mutations, Nature Genetics, 53, 342–353.

D. Sun, S. He, W. F. D. Bennett, C. L. Bilodeau,O. S. Andersen, F. C. Lightstone, H. I. Ingolfsson (2021) Atomistic Characterization of Gramicidin Channel Formation, J. Chem. Theory Comput., 17, 1, 7–12.

D. Sun, T. A. Peyear, W. F. D. Bennett, M. Holcomb, S. He, F. Zhu, F. C. Lightstone, O. S. Andersen and Helgi I. Ingólfsson (2020) Assessing the Perturbing Effects of Drugs on Lipid Bilayers using Gramicidin Channel-Based in Silico and in Vitro Assays. J. Med. Chem. 63, 11809-11818.

W. F. D. Bennett, S. He, C. L. Bilodeau, D. Jones, D. Sun, H. Kim, J. E. Allen, F. C. Lightstone, H. I. Ingolfsson (2020) Predicting Small Molecule Transfer Free Energies by Combining Molecular Dynamics Simulations and Deep Learning. J. Chem. Inf. Model., 60, 11, 5375-5381.

H. I. Ingólfsson, H. Bhatia, T. Zeppelin, W. F. D. Bennett, K. A. Carpenter, P.-C. Hsu, G. Dharuman, P.-T. Bremer, B. Schiøtt, F. C. Lightstone, and T. S. Carpenter (2020) Capturing Biologically Complex Tissue-Specific Membranes at Different Levels of Compositional Complexity. J. Phys. Chem. B, 124, 36, 7819–7829.

X. Zhang, S. Sundram, T. Oppelstrup, S. I. L. Kokkila-Schumacher, T. S. Carpenter, H. I. Ingolfsson, F. H. Streitz, F. C. Lightstone, J. N. Glosli (2020)  ddcMD:A Fully GPU-accelerated Molecular Dynamics Program for the Martini Force Field. J. Chem. Phys., 153, 045103.

F. Zhu, X. Zhang, J. E. Allen, D. Jones, F. C. Lightstone (2020) Binding Affinity Prediction by Pairwise Function Based on Neural Network. J. Chem. Inf. Model. 60, 2766-2772.

W. R. Martin, F. C. Lightstone, F. Cheng (2020) In Silico Insights into Protein-protein Interaction Disruptive Mutations in the PCSK9-LDLR Complex. International Journal of Molecular Sciences. 21(5), 1550.

V. Ovchinnikov, S. Conti, E. Y. Lau, F. C. Lightstone, M. Karplus (2020) Microsecond molecular dynamics simulations of proteins using a quasi-equilibrium solvation shell model. J. Chem.Theory Comput., 16, 3, 1866–1881.

D. Goswami, D. Chen, Y. Yang, P. R. Gudla, J. Columbus, K.Worthy, M. Rigby, M. Wheeler, S. Mukhopadhyay, K. Powell, W. Burgan, V. Wall, D. Esposito, D. Simanshu, F. C. Lightstone, D. V. Nissley, F. McCormick, T. Turbyville (2020) Membrane Interactions of the G-domain and the HVR of KRAS4b Defines Its Unique Diffusion BehavioreLife, In press.

F. Di Natale, H. Bhatia, T. S. Carpenter, C. Neale, S. Kokkila Schumacher, T. Oppelstrup, L. Stanton, X. Zhang, S. Sundram, T. R. W. Scogland, G. Dharuman, M. P. Surh, Y. Yang, C. Misale, L. Schneidenbach, C. Costa, C. Kim, B. D’Amora, S. Gnanakaran, D. V. Nissley, F. Streitz, F. C. Lightstone, P.-T. Bremer, J. N. Glosli, H. I. Ingolfsson (2019) A Massively Parallel Infrastructure for Adaptive Multiscale Simulations: Modeling RAS Initiation Pathway for Cancer. SC '19: Proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis, Article No.: 57, 1–16. (won Best Paper)

D. Sun, T. A. Peyear, W. F. D. Bennett, O. S. Andersen, F. C. Lightstone, H. I. Ingolfsson (2019) Molecular Mechanism for Gramicidin Dimerization and Dissociation in Bilayers of Different Thickness. Biophys. J., 117, 1831–1844.

H. Bhatia, H. I. Ingolfsson, T. S. Carpenter, F. C. Lightstone, P.-T. Bremer (2019) MemSurfer: A Tool for Robust Computation and Characterization of Curved Membranes.  J. Chem.Theory Comput., 15, 11, 6411-6421.

H. Y. H. Tang, D. S. Shin, G. L. Hura, Y. Yang, X. Hu, F. C. Lightstone, M. D. McGee, H. S. Padgett, S. M. Yannone, and J. A. Tainer (2018) Structural control of nonnative ligand binding in engineered mutants of phosphoenolpyruvate carboxykinase.  Biochemistry, Just Accepted.

T. S. Carpenter, C. A. López, C. Neale, C. Montour, H. I. Ingólfsson, F. Di Natale, F. C. Lightstone, and S. Gnanakaran (2018) Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force FieldJournal of Chemical Theory and Computation14, (11) 6050-6062.

J. M. Witkin, R. A. Shenvi, X. Li, S. D. Gleason, J. Weiss, D. Morrow, J. T. Catow, M. Wakulchik, M. Ohtawa, H-H. Lu, M. D. Martinez, J. M. Schkeryantz, T. S. Carpenter, F. C. Lightstone, R. Cerne (2018) Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide reveals a non-convulsant signature and potential for progression in neurodegenerative disease studiesBiochemical Pharmacology, 155, 61-70.

J. P. Cranford, T. J. O’Hara, C. T. Villongco, O. M. Hafez, R. C. Blake, J. Loscalzo, J.-L. Fattebert, D. F. Richards, X. Zhang, J. N. Glosli, A. D. McCulloch, D. E. Krummen, F. C. Lightstone, S. E. Wong (2018) Efficient Computational Modeling of Human Ventricular Activation and Its Electrocardiographic Representation: A Sensitivity StudyCardiovascular Engineering and Technology,  9, 447-467.

H. I. Ingólfsson, T. S. Carpenter, H. Bhatia, P.-T. Bremer, S. J. Marrink, and F. C. Lightstone (2017) Computational lipidomics of the neuronal plasma membraneBiophysics Journal113 (10), 2271-2280.

M. A. Malfatti, H. A. Enright, N. A. Be, E. A. Kuhn, S. Hok, M. W. NcNerney, V. Lao, T. H. Nguyen, F. C. Lightstone, T. S. Carpenter, B. J. Bennion, C. A. Valdez (2017) The biodistribution and pharmacokinetics of the oxime acetylcholinesterase reactivator RS194B in guinea pigsChemico-Biological Interactions277, 159-167.

F. Qian, C. Huang, Y.-D. Lin, A. N. Ivanovskaya, T. J. O'Hara, R. H. Booth, C. J. Creek, H. A. Enright, D. A. Soscia, A. M. Belle, R. Liao, F. C. Lightstone, K. S. Kulp and E. K. Wheeler (2017) Simultaneous electrical recording of cardiac electrophysiology and contraction on chip.  Lab on a Chip, 17, 1732-1739.

B. J. Bennion, N. A. Be, M. W. McNerney, V. Lao, E. M. Carlson, C. A. Valdez, M. A. Malfatti, H. A. Enright, T. H. Nguyen, F. C. Lightstone, and T. S Carpenter (2017) Predicting a Drug’s Membrane Permeability: A Computational Model Validated With In Vitro Permeability Assay Data.  J. Phys. Chem. B, 121 (20), 5228–5237.

X. Zhang, H. Perez-Sanchez, F. C. Lightstone (2017) A Comprehensive Docking and MM/GBSA Rescoring Study of Ligand Recognition upon Binding Antithrombin.  Current Topics in Medicinal Chemistry, 171-9.

T. S. Carpenter and F. C. Lightstone (2016) An Electrostatic Funnel in the GABA-Binding Pathway.  PLoS Comput. Biol.12(4): e1004831.

A. Navid, D. M. Ng, S. E. Wong, F. C. Lightstone (2016) Application of a physiology-based pharmacokinetic model to study theophylline metabolism and its interactions with ciprofloxacin and caffeineCPT: Pharmacometrics & Systems Pharmacology5 (2), 74-81.

R. A. Kelsey, D. A. Miller, S. R. Parkin, K. Liu, J. E. Remias, Y. Yang, F. C. Lightstone, K. Liu, C. A. Lippert, S. A. Odom, (2016) Carbonic Anhydrase Mimics for Enhanced CO2 Absorption in an Amine-Based Capture SolventDalton Transactions45, 324-333.

J.-L. Fattebert, E. Y. Lau, B. J. Bennion, P. Huang, and F. C. Lightstone (2015)  Large-scale First-Principles molecular dynamics simulations with electrostatic embedding: application to acetylcholinesterase catalysisJ. Chem. Theory Comput., 115688–5695.

B. J. Bennion, S. G. Essiz, E. Y. Lau, J.-L. Fattebert, A. Emigh, F. C. Lightstone (2014) A Wrench in the Works of Human Acetylcholinesterase: Soman Induced Conformational Changes Revealed by Molecular Dynamics SimulationsPLoS ONE10(4): e0121092.

X. Zhang, H. Péréz-Sánchez, and F. C. Lightstone. (2015) Molecular Dynamics Simulations of Ligand Recognition Upon Binding Antithrombin: A MM/GBSA ApproachBioinformatics and Biomedical Engineering9044, 584-593.

M. X. LaBute, X. Zhang, J. Lenderman, B. J. Bennion, S. E. Wong, F. C. Lightstone (2014) Adverse Drug Reaction Prediction Using Scores Produced by Large-Scale Drug-Protein Target Docking on High-Performance Computing MachinesPLoS ONE9(9): e106298.

T. S. Carpenter, D. A. Kirshner, E. Y. Lau, S. E. Wong, J. P. Nilmeier, and F. C. Lightstone (2014) A Method to Predict Blood-Brain Barrier Permeability of Drug-like Compounds Using Molecular Dynamics SimulationsBiophys. J.107(3), 630-641.

C. Zhao, S. H. Hwang, B. A. Buchholz , T. S. Carpenter, F. C. Lightstone, J. Yang, B. D. Hammock, J. E. Casida (2014) The GABAA Receptor Target of TetramethylenedisulfotetramineProc. Natl. Acad. Sci. USA, 111(23), 8607-8612.

Y. Yang, S. E. Wong and F. C. Lightstone (2014) Understanding a Substrate’s Product Regioselectivity in a Family of Enzymes:  A Case Study of Acetaminophen Binding in Cytochrome P450s. PLoS ONE9(2): e87058.

H. J. Kulik, S. E. Wong, S. E. Baker, C. A. Valdez, J. H. Satcher, R. D. Aines, and F. C. Lightstone (2014) Developing an approach for first-principles catalyst design: application to carbon capture catalysisActa Crystallographica, C70, 123-131. 

X. Zhang, S. E. Wong, F. C. Lightstone (2014) Toward Fully Automated High Performance Computing Drug Discovery: A Massively Parallel Virtual Screening Pipeline for Docking and Molecular Mechanics/Generalized Born Surface Area Rescoring to Improve Enrichment. J. Chem. Inf. Model., 54(1) 324-337.

L. W. Tari, X. Li, M. Trzoss, D. C. Bensen, Z. Chen, T. Lam, J. Zhang, S. J. Lee, G. Hough, D. Phillipson, S. Akers-Rodriguez, M. L. Cunningham, B. P. Kwan, K. J. Nelson, A. Castellano, J. B. Locke, V. Brown-Driver, T. M. Murphy, V. S. Ong, C. M. Pillar, D. L. Shinabarger, J. Nix, F. C. Lightstone, S. E. Wong, T. B. Nguyen, K. J. Shaw, J. Finn (2013) Tricyclic GyrB/ParE (TriBE) Inhibitors: A New Class of Broad-Spectrum Dual-Targeting Antibacterial Agents. PLoS ONE, 8(12): e84409.

L. Koziol, N. Kumar, S. E. Wong, F. C. Lightstone (2013) Molecular Recognition of Aromatic Rings by Flavin: Electrostatics and Dispersion Determine Ring Positioning Above IsoalloxazineJ. Phys. Chem. A, 117, 12946-12952.

A. Navid, D. M. Ng, B. J. Stewart, S. E. Wong, and F. C. Lightstone (2013) Quantitative In Silico Analysis of Transient Metabolism of Acetaminophen and Associated Causes of Hepatotoxicity in Humans. In Silico Pharmacology, 1, 14. 

T. S. Carpenter, E. Y. Lau, and F. C. Lightstone (2013) Identification of a Possible Secondary Picrotoxin-Binding Site on the GABAA-ReceptorChemical Research in Toxicology26, 1444-1454.

B. J. Bennion, E. Y.  Lau, J.-L. Fattebert, P. Huang, E. Schwegler, W. Corning, F. C. Lightstone (2013) Modeling the Binding of CWAs to AChE and BuChE. Military Medical Science Letters, vol. 82(3), p. 102-114.

E. Y. Lau, S. E. Wong, S. E. Baker, J. P. Bearinger, L. Koziol, C. A. Valdez, J. H. Satcher Jr, R. D. Aines and F. C. Lightstone (2013) Comparison and Analysis of Zinc and Cobalt-based Systems as Catalytic Entities for the Hydration of Carbon Dioxide. PLoS ONE, 8(6): e66187.

D. A. Kirshner, J. P. Nilmeier, and F. C. Lightstone (2013) Catalytic Site Identification – A Web Server to Identify Catalytic Site Structural Matches Throughout PDB. Nucleic Acids Research, 41, W256-W265 

J. P. Nilmeier, D. A. Kirshner, S. E. Wong, and F. C. Lightstone (2013) Rapid Catalytic Template Searching as an Enzyme Function Prediction ProcedurePLoS ONE, 8(5), e62535.

X. Zhang, S. E. Wong, F. C. Lightstone (2013) Message Passing Interface and Multithreading Hybrid for Parallel Molecular Docking of Large Databases on Petascale High Performance Computing Machines. J. Comput. Chem., 34, 915-927.

L. Koziol, S. G. Essiz, S. E. Wong, E. Y. Lau, C. A. Valdez, J. H. Satcher, Jr., R. D. Aines, F. C. Lightstone (2013) Computational Analysis of a Zn-bound Tris(imidazolyl) Calix[6]arene Aqua Complex:  Toward Incorporating Second-coordination Sphere Effects into Carbonic Anhydrase Biomimetics. J. Chem. Theory. Comput., 9, 1320–1327.

Y. Yang, F. C. Lightstone, S. E. Wong (2013) Solvents in Structure-Based in Drug Discovery. Expert Opinion On Drug Discovery, 8, 277-287.

M. Trzoss, D. C. Bensen, X. Li, Z. Chen, T. Lam, J. Zhang, C. J. Creighton, M. L. Cunningham, B. Kwan, M. Stidham, K. Nelson, V. Brown-Driver, A. Castellano, K. J. Shaw, F. C. Lightstone, S. E. Wong, T. B. Nguyen, J. Finn, L. W. Tari (2013) Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: Development of inhibitors with broad spectrum, Gram-negative antibacterial activityBioorg. Med. Chem. Lett., 23, 1537-1543.L.

W. Tari, M. Trzoss, D. C. Bensen, X. Li, Z. Chen, T. Lam, J. Zhang, C. J. Creighton, M. L. Cunningham, B. Kwan, M. Stidham, K. J. Shaw, F. C. Lightstone, S. E. Wong, T. B. Nguyen, J. Nix, J. Finn (2013) Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activityBioorg. Med. Chem. Lett., 23, 1529-1536.

W. H. Benner, G. S. Lewis, S. V. Hering, B. Segelke, M. Corzett, J. E. Evans and F. C. Lightstone (2012) Re-Electrospraying Splash-Landed Proteins and Nanoparticles. Analytical Chemistry, 84, 2498-2504.