Gregory A. Voth

Research Interests:

The research in the Voth group involves theoretical and computer simulation studies of biomolecular and liquid state phenomena, as well as of novel materials. A primary goal of this effort is the development and application of new theory and computational methodologies to explain and predict the behavior of complex systems (see figure below). Such methods are developed, for example, to probe phenomena such as protein-protein self-assembly, membrane-protein interactions, biomolecular and liquid state charge transport, complex fluids and self-assembly. Specific examples of research projects include:

Multiscale Theory and Simulation: The Voth group has a key focus on the development of powerful multiscale theory and computational methods for complex biomolecular and other soft matter systems (see figure below). These multiscale methods include systematic coarse-graining approaches, mesoscopic modeling, and multiscale bridging between all of the relevant scales. Our multiscale methods are being applied to actin filaments, microtubules, biological membranes and membrane proteins, nucleic acids, peptide aggregation and self-assembly, viral capsids, liquids, and polymers.

Charge Transport: The transport of charge (protons and electrons) in aqueous and biomolecular systems is another important multiscale phenomenon. Here, the smallest scale is at the scale of the electrons because such processes involve either the electrons directly or indirectly, often in the form of proton transport (via, for example, the Grotthuss hopping mechanism in which chemical bonds and hydrogen bonds along the water chain are rearranged to translocate the excess protonic charge). Proton transport is also dependent on the conformation, dynamics, and assembly of the medium in which it occurs. Our group has worked for more than twenty years to develop a multiscale theoretical and computational methodology to describe proton transport phenomena in biology and in a host of other systems, at large times and length scales. Schematically depicted in the figure below is the range of the systems we have studied. Our group also carries out theoretical and computational studies of charge solvation phenomena and dynamics in materials such as proton and hydroxide exchange membranes (e.g., for fuel cell applications), as well as in complex liquids such as electrolytes and room temperature ionic liquids.

Fundamental Quantum Theory: The Voth group has a long-standing interest in the development of new quantum mechanical perspectives and methods for quantum dynamics, kinetics, and statistical mechanics. Most recently, we have begun to explore the meaning(s) of coarse-graining in quantum mechanics, first for quantum statistical mechanics (see figure below) and in the future for condensed phase quantum dynamics.

Recent Publications

Accepted

J. Beiter and G. A. Voth, “Making the Cut: Multiscale Simulation of Membrane Remodeling,” Curr. Opin. Struct. Biol. (in press)

F. Aydin^#, H. H. Katkar^#, A. Morganthaler^#, A. J. Harker, D. R. Kovar, and G. A. Voth, Cytoskeleton (in press). (^#Authors contributed equally)

Y. Liu, C. Li, M. Gupta, R. M. Stroud, and G. A. Voth, “Kinetic Network Modeling with Molecular Simulation Inputs: A Proton-Coupled Phosphate Symporter”, Biophys. J. (in press) 

Published

Y. Chen, X. Ma, J. H. Hack, S. Zhang, A. Peng, J. P. Dombrowski, G. A. Voth, A. Tokmakoff, M. C. Kung, and H. H. Kung, “Molecular Tuning of Reactivity of Zeolite Protons in HZSM-5”, J. Am. Chem. Soc. 146, 10342-10356 (2024).

P. Banerjee, V. Monje-Galvan, and G. A. Voth, “Cooperative Membrane Binding of HIV-1 Matrix Proteins”, J. Phys. Chem. B 128, 2595­–2606 (2024). PMCID: PMC10962350

P. Banerjee, K. Qu, J. A. G. Briggs, and G. A. Voth, “Molecular Dynamics Simulations of HIV-1 Matrix-Membrane Interactions at Different Stages of Viral Maturation,” Biophys. J. 123, 389–406 (2024). PMCID: PMC10870173

A. Hudait and G. A. Voth, “HIV-1 Capsid Shape, Orientation, and Entropic Elasticity Regulate Translocation into the Nuclear Pore Complex”, Proc. Nat. Acad. Sci. USA 121, e2313737121(1-12) (2024). PMCID: PMC10823262

B. Yoon, S. Chen, and G. A. Voth, “On the Key Influence of Amino Acid Ionic Liquid Anions on CO₂ Capture”, J. Am. Chem. Soc. 146, 1612−1618 (2024). PMCID:PMC10798249

P. Banerjee and G. A. Voth, “Conformational Transitions of the HIV-1 Gag Polyprotein Upon Multimerization and gRNA Binding”, Biophys. J. 123, 42–56 (2024).PMCID: PMC10808027

T. D. Loose,*P. G. Sahrmann,* T. S. Qu, and G. A. Voth, “Coarse-Graining with Equivariant Neural Networks: A Path Towards Accurate and Data-Efficient Structural Models”, J. Phys. Chem. B 127, 10564–10572 (2023). (*Authors contributed equally). PMCID: PMC10726966  

J. Wu,* W. Xue,* and G. A. Voth, “K-Means Clustering Coarse-graining (KMC-CG): A Next Generation Methodology for Determining Optimal Coarse-grained Mappings of Large Biomolecules”, J. Chem. Theory Comp. 19, 8987−8997 (2023). (*Authors contributed equally). PMCID: PMC10720621

K. Ghosh, T. D. Loose, and G. A. Voth, “Can a Coarse-grained Water Model Capture the Key Physical Features of the Hydrophobic Effect?”, J. Chem. Phys. 159, 224105(1-12) (2023).

J. Jin, J. Hwang, and G. A. Voth, “Gaussian Representation of Coarse-Grained Interactions of Liquids: Theory, Parametrization, and Transferability”, J. Chem. Phys. 159, 184105(1-27) (2023).

J. Jin, E. K. Lee, and G. A. Voth, “Understanding Dynamics in Coarse-Grained Models: III. Roles of Rotational Motion and Translation-Rotation Coupling in Coarse-Grained Dynamics”, J. Chem. Phys. 159, 164102(1-16) (2023).

Y. Peng, A. J. Pak, A. E. P. Durumeric, P. G. Sahrmann, S. Mani,J. Jin, T. D. Loose, J. Beiter, and G. A. Voth, “OpenMSCG: A Software Tool for Bottom-up Coarse-graining”, J. Phys. Chem. B 127, 8537–8550 (2023). PMCID: PMC10577682

J. H. Hack, X. Ma, Y. Chen, J. P. Dombrowski, N. H. C. Lewis, C. Li, H. H. Kung, G. A. Voth, and A. Tokmakoff, “Proton Dissociation and Delocalization Under Stepwise Hydration of Zeolite HZSM‑5”, J. Phys. Chem. C 127, 16175–16186 (2023).

B. Yoon and G. A. Voth, “Elucidating the Molecular Mechanism of CO₂ Capture by Amino Acid Ionic Liquids”, J. Am. Chem. Soc. 145, 15663−15667 (2023).  PMCID: PMC10375530

P. G. Sahrmann, T. D. Loose, A. E.P. Durumeric, and G. A. Voth, “Utilizing Machine Learning to Greatly Expand the Range and Accuracy of Bottom-Up Coarse-Grained Models Through Virtual Particles”, J. Chem. Theory Comp. 19, 4402−4413 (2023). PMCID: PMC10373655

A. Hudait, J.H. Hurley,and G. A. Voth, “Organization of Upstream ESCRT Machinery at the HIV-1 Budding Site”, Biophys. J. 122, 2655–2674(2023). PMCID: PMC10397573

G. A. Voth and T. Haliloglu, “Deciphering the Dynamic Codes: Advances in Biomolecular Modeling and Simulation”, Curr. Opin. Struct. Biol. 81, 102642 (2023).

D. Beckett and G. A. Voth, “Unveiling the Catalytic Mechanism of GTP Hydrolysis in Microtubules”, Proc. Nat. Acad. Sci. USA 120, e2305899120 (2023). PMCID: PMC10319017

K. Wang, C. W. Lee, X. Sui, S. Kim, S. Wang, A. B. Higgs, A. J. Baublis, G. A Voth, M. Liao, T. Walther, R. Farese, Jr, “The Structure of Phosphatidylinositol Remodeling MBOAT7 Reveals Its Catalytic Mechanism and Enables Inhibitor Identification”, Nature Comm. 14, 3533 (2023). PMCID: PMC10267149 

A. E. P. Durumeric and G. A. Voth, “Using Classifiers to Understand Coarse-grained Models and Their Fidelity With the Underlying All-Atom Systems”, J. Chem. Phys. 158, 234101(1-15) (2023).

H. T. Kratochvil, L. C. Watkins, M.  Mravic, J. L. Thomaston, J.M. Nicoludis, N. H. Somberg,L. Liu, M. Hong, G. A. Voth, and W. F. DeGrado, “Transient Water Wires Mediate Selective Proton Conduction in Designed Channel Proteins”, Nature Chem. 15, 1012–1021 (2023).PMCID: PMC10475958

S. Chen, Z. Li and G. A. Voth, “Acidic Conditions Impact Hydrophobe Transfer Across the Oil-Water Interface in Unusual Ways”, J. Phys. Chem. B 127, 3911−3918 (2023). PMCID: PMC10166083

T. C. Walther, S. Kim, H. Arlt, G. A. Voth, and R. V. Farese, Jr., “Structure and Function of Lipid Droplet Assembly Complexes”, Curr. Opin. Struct. Biol. 80, 102606(1-8)(2023). PMCID: PMC10853036

J. Jin and G. A. Voth, “Statistical Mechanical Design Principles for Coarse-grained Interactions Across Different Conformational Free Energy Surfaces”, J. Phys. Chem. Lett. 14, 1354-1362 (2023).PMCID: PMC9940719

Z. Yue, C. Li, and G. A. Voth, “The Role of Conformational Change and Key Glutamic Acid Residues in the ClC-ec1 Antiporter”, Biophys. J. 122, 1068–1085(2023). PMCID: PMC10111279

S. Chen and G. A. Voth, “How Does Electronic Polarizability or Scaled-Charge Affect the Interfacial Properties of Room Temperature Ionic Liquids?”, J. Phys. Chem B 127, 1264-1275 (2023). PMCID: PMC9924258

J. Jin, K. S. Schweizer, and G. A. Voth, “Understanding Dynamics in Coarse-Grained Models: I. Universal Excess Entropy Scaling Relationship”, J. Chem. Phys. 158, 034103(1-17) (2023).

J. Jin, K. S. Schweizer, and G. A. Voth, “Understanding Dynamics in Coarse-Grained Models: II. Coarse-Grained Diffusion Modeled Using Hard Sphere Theory”, J. Chem. Phys. 158, 034104(1-18) (2023).

M. Gupta, A. J. Pak, and G. A. Voth, “Critical Mechanistic Features of HIV-1 Viral Capsid Assembly” Science Adv. 9, eadd7434 (2023). PMCID: PMC9821859

Y. Liu, C. Li, and G. A. Voth, “A Generalized Transition State Theory Treatment of Water-Assisted Proton Transport Processes in Proteins”, J. Phys. Chem. B 126, 10452-10459 (2022). PMID: 36459423; PMCID: PMC9762399

G. Wei, N. Iqbal, V. V. Courouble, A. C. Francis, P. K. Singh, A. Hudait, A. S. Annamalai, S. Bester, S.-W. Huang, N. Shkriabai, L. Briganti, R. Haney^, V. N. KewalRamani, G. A. Voth, A. N. Engelman, G. B. Melikyan, P. R. Griffin, F. Asturias, and M. Kvaratskhelia, “Prion-Like Low Complexity Regions Enable Avid Virus-Host Interactions During HIV-1 Infection”,Nature Comm. 13, 5879 (2022). PMCID: PMC 9537594

K.Dolan, M. Dutta, D. M. Kern, A. Kotecha, G. A. Voth, and S. G. Brohawn, “Cryo-EM Structure of SARS-CoV-2 M Protein in Lipid Nanodiscs”, eLife  11, e81702 (2022). PMCID: PMC9642992

F.-C. Tsai,J. M. Henderson, Z. Jarin, E. Kremneva, Y. Senju, J. Pernier, O. Mikhajlov, J. Manzi, C. Le Clainche, G. A. Voth, P. Lappalainen, and Patricia Bassereau, “Activated IRSp53 Clustering Controls the Formation of VASP-Actin-Based Membrane Protrusions”, Science Adv. 8, eabp8677(2022).PMCID:PMC9565809

T. D. Loose, P. G. Sahrmann, and G. A. Voth, “Centroid Molecular Dynamics Can Be Greatly Accelerated Through Neural Network Learned Centroid Forces Derived from Path Integral Molecular Dynamics”, J. Chem. Theory Comp. 18, 5856−5863 (2022). PMCID: PMC9558744

J. Jin, A.J. Pak, A. E. P. Durumeric, T. D. Loose, and G. A. Voth “Bottom-Up Coarse-Graining: Principles and Perspectives”, J. Chem. Theory Comp. 18, 5759-5791 (2022). PMCID: PMC9558379

J. Zuchniarz, Y. Liu, C. Li, and G. A. Voth, “Accurate Calculations in Proteins with Reactive Molecular Dynamics Provide Physical Insight Into the Electrostatic Origins of Their Values”, J. Phys. Chem. B 126, 7321-7330 (2022). PMCID: PMC9528908

W. H. Ryu and G. A. Voth, “Coarse-graining of Imaginary Time Feynman Path Integrals: Inclusion of Intramolecular Interactions and Bottom-up Force-matching”, J. Phys. Chem. A 126, 6004–6019 (2022). PMCID: PMC9466601 

C. Li, Z. Yue, S. Newstead, and G. A. Voth, “Proton Coupling and the Multiscale Kinetic Mechanism of a Peptide Transporter”, Biophys. J. 121, 2266–2278 (2022). PMCID: PMC9279349

A. J. Pak, M. Gupta, M. Yeager,and G. A. Voth, “Inositol Hexakisphosphate (IP6) Accelerates Immature HIV-1 Gag Protein Assembly Towards Kinetically-Trapped Morphologies”, J. Am Chem. Soc. 144, 10417–10428 (2022). PMCID: PMC9204763

S. Kim, J. Chung,H. Arlt, A. J. Pak, R. V. Farese, Jr,T. C. Walther, and G. A. Voth, “Seipin Transmembrane Segments Critically Function in Triglyceride Nucleation and Lipid Droplet Budding from the Membrane”, eLife 11, e75808 (2022). PMCID: PMC9122495

C. Li, F. Paesani, and G. A. Voth, “Static and Dynamic Correlations in Water: Comparison of Classical Ab Initio Molecular Dynamics at Elevated Temperature With Path Integral Simulations at Ambient Temperature”, J. Chem. Theory Comp. 18, 2124-2131 (2022). PMCID: PMC9059465

Z. Yue,* Z. Wang,*and G. A. Voth, “Ion Permeation, Selectivity, and Electronic Polarization in Fluoride Channels”, Biophys. J. 121, 1336–1347(2022). (*Authors contributed equally) PMCID: PMC9034187

S. Kim, J. M. J. Swanson, and G. A. Voth, “Computational Studies of Lipid Droplets”, J. Phys. Chem. B 126, 2145-2154 (2022). (Feature Article). PMCID: PMC8957551; Addition and Correction: 128, 16, 4033.

A. Yu, E. M.Y. Lee, J. A.G. Briggs, B. K. Ganser-Pornillos, O. Pornillos, and G. A. Voth, “Strain and Rupture of HIV-1 Capsids During Uncoating”, Proc. Nat. Acad. Sci. USA 119, e2117781119(1-8) (2022). PMCID: PMC8915963

A. J. Pak, A. Yu, Z. Ke, J. A. G. Briggs, and G. A. Voth, “Cooperative Multivalent Receptor Binding Promotes Exposure of the SARS-CoV-2 Fusion Machinery Core”, Nature Comm. 13, 1002 (2022). PMCID: PMC8863989

S. Kim, C. Li, R. V. Farese, Jr, T. C. Walther, and G. A. Voth, “Key Factors Governing Initial Stages of Lipid Droplet Formation”, J. Phys. Chem. B 126, 453–462 (2022). PMCID: PMC8922452

C. Li and G. A. Voth, “Using Machine Learning to Greatly Accelerate Path Integral Ab Initio Molecular Dynamics”, J. Chem. Theory Comp. 18, 599-604 (2022). PMCID: PMC8864787

L. C. Watkins, W. F. DeGrado, and G. A. Voth, “Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior”, J. Am. Chem. Soc. 144, 769−776 (2022). PMCID: PMC8834648