The Biochemical and Biophysical Systems Group’s scientists use cutting-edge, multi-scale, in silico simulations to tackle problems in biology. We use a wide range of computational biology methods that employ LLNL’s high-performance computing resources to simulate systems from sub-atomic scale to population level. These methods include atomistic and coarse-grained molecular dynamics, quantum simulations, constraint-based genome-scale simulations, reaction-transport dynamic simulations, and agent-based, whole-organ, and pharmacokinetics/pharmacodynamics models. We develop new computational methods to describe and predict biological systems. In addition, we combine experimental efforts with physics-based simulations and statistical and machine-learning models to accelerate the design and development of safe and effective therapeutics. Overall, we seek predictive understanding of protein-mediated processes related to critical missions of LLNL, including bioenergy, medical countermeasures, and new materials.
Structural control of nonnative ligand binding in engineered mutants of phosphoenolpyruvate carboxykinase
Henry Yue Hin Tang, David S Shin, Gregory L. Hura, Yue Yang, Xiaoyu Hu, Felice C Lightstone, Matthew D McGee, Hal S Padgett, Steven M Yannone, and John A. Tainer
Biochemistry (2018) Just Accepted.
Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse-Grained Force Field
Timothy S. Carpenter, Cesar A. López, Christopher Neale, Cameron Montour, Helgi Ingólfur Ingólfsson, Francesco Di Natale, Felice C. Lightstone, and Sandrasegaram Gnanakaran
Journal of Chemical Theory and Computation (2018) 14, (11) 6050-6062.
Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide reveals a non-convulsant signature and potential for progression in neurodegenerative disease studies
Jeffrey M. Witkin, Ryan A. Shenvi, Xia Li, Scott D. Gleason, Julie Weiss, Denise Morrow, John T. Catow, Mark Wakulchik, Masaki Ohtawa, Hai-Hua Lu, Michael D. Martinez, Jeffrey M. Schkeryantz, Timothy S. Carpenter, Felice C. Lightstone, Rok Cerne
Biochemical Pharmacology (2018) 155, 61-70.
Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications
Sean F. Gilmore, Timothy S. Carpenter, Helgi I. Ingolfsson, Sandra K. G. Peters, Paul T. Henderson, Craig D. Blanchette, Nicholas O. Fischer
Nanoscale (2018) 10, 7420-7430.
Efficient Computational Modeling of Human Ventricular Activation and Its Electrocardiographic Representation: A Sensitivity Study
Johathan P. Cranford, Thomas J. O’Hara, Christopher T. Villongco, Omar M. Hafez, Robert C. Blake, Joseph Loscalzo, Jean-Luc Fattebert, David F. Richards, Xiaohua Zhang, James N. Glosli, Andrew D. McCulloch, David E. Krummen, Felice C. Lightstone, Sergio E. Wong
Cardiovascular Engineering and Technology (2018) 9, Online First.
Computational lipidomics of the neuronal plasma membrane
Helgi I. Ingólfsson, Timothy S. Carpenter, Harsh Bhatia, Peer-Timo Bremer, Siewert J. Marrink, Felice C. Lightstone
Biophysics Journal (2017) 113 (10), 2271-2280.
The biodistribution and pharmacokinetics of the oxime acetylcholinesterase reactivator RS194B in guinea pigs
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
Chemico-Biological Interactions (2017) 277, 159-167.
Simultaneous electrical recording of cardiac electrophysiology and contraction on chip
Fang Qian, Chao Huang, Yi-Dong Lin, Anna N. Ivanovskaya, Thomas J. O'Hara, Ross H. Booth, Cameron J. Creek, Heather A. Enright, David A. Soscia, Anna M. Belle, Ronglih Liao, Felice C. Lightstone, Kristen S. Kulp and Elizabeth K. Wheeler
Lab on a Chip (2017) 17, 1732-1739.
Predicting a Drug’s Membrane Permeability: A Computational Model Validated With In Vitro Permeability Assay Data
Brian J. Bennion, Nicholas A. Be, Margaret Windy McNerney, Victoria Lao, Emma M. Carlson, Carlos A. Valdez, Michael A. Malfatti, Heather A. Enright, Tuan H Nguyen, Felice C Lightstone, and Timothy S. Carpenter
J. Phys. Chem. B (2017) 121 (20), 5228-5237.
Re-directing bacterial microcompartment systems to enhance recombinant expression of lysis protein E from bacteriophage ϕX174 in Escherichia coli
Mimi C. Yung, Feliza A. Bourguet, Timothy S. Carpenter and Matthew A. Coleman
Microb. Cell Fact. (2017) 16 (71).
A Comprehensive Docking and MM/GBSA Rescoring Study of Ligand Recognition upon Binding Antithrombin
Xiaohua Zhang, Horacio Perez-Sanchez, and Felice C. Lightstone
Current Topics in Medicinal Chemistry (2017) 17, 1-9.
The Free Energy of Small Solute Permeation through the Escherichia coli Outer Membrane Has a Distinctly Asymmetric Profile
Tim Carpenter, Jamie Parkin, and Syma Khalid
J. Phys. Chem. Lett. (2016) 7(17): p. 3446-3451.
Molecular dynamics simulations reveal the conformational flexibility of Lipid II and its loose association with the defensin plectasin in the Staphylococcus aureus membrane
Sarah Witzke, Michael Petersen, Tim Carpenter, Syma Khalid
Biochemistry (2016) 55(23): 3303-3314.
Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches toward Remediation Technologies of Warfare Agents and Pesticides
Teodorico C. Ramalho, Alexandre A. de Castro, Daniela R. Silva, Maria Cristina Silva, Tanos C. C. Franca, Brian J. Bennion and Kamil Kuca
Current Medicinal Chemistry (2016) 23, 1041-1061.
An Electrostatic Funnel in the GABA-Binding Pathway
Timothy S. Carpenter and Felice C. Lightstone
PLoS Comput. Biol. (2016) 12(4): e1004831.
Solution-State Structure and Affinities of Cyclodextrin:Fentanyl Complexes by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation
Brian P. Mayer, Daniel J. Kennedy, Edmond Y. Lau, Carlos A. Valdez
Journal of Physical Chemistry B (2016) 120(9), 2423-2433.
Application of a Physiologically-based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions with Ciprofloxacin and Caffeine
A. Navid, D. M. Ng, S. E. Wong, F. C. Lightstone
CPT: Pharmacometrics & Systems Pharmacology (2016) 5 (2), 74-81.
Shock Wave-Induced Damage of a Protein by Void Collapse
Edmond Y. Lau, Max L. Berkowitz, Eric Schwegler
Biophysical Journal (2016) 110(1), 147–156.
Carbonic Anhydrase Mimics for Enhanced CO2 Absorption in an Amine-Based Capture Solvent
Rachael A. Kelsey, David A. Miller, Sean R. Parkin, Kun Liu, Joe E. Remias, Yue Yang, Felice C. Lightstone, Kunlei Liu, Cameron A. Lippert and Susan A. Odom
Dalton Transactions (2016) 45, 324-333.