James C. Gumbart
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View article: Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly
Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly Open
Molecular dynamics (MD) simulations provide a detailed description of biophysical processes, allowing mechanistic questions to be addressed at the atomic level. The promise of such approaches is partly hampered by well-known sampling issue…
View article: The dynamic lateral gate of the mitochondrial β-barrel biogenesis machinery is blocked by darobactin A
The dynamic lateral gate of the mitochondrial β-barrel biogenesis machinery is blocked by darobactin A Open
The folding and insertion of β-barrel proteins into the mitochondrial outer membrane is facilitated by the s orting and a ssembly m achinery (SAM) complex. Here we report two 2.8 Å cryo-EM structures of the Thermothelomyces thermophilus SA…
View article: Structural modeling reveals the mechanism of motor ATPase coordination during type IV pilus retraction
Structural modeling reveals the mechanism of motor ATPase coordination during type IV pilus retraction Open
Diverse bacterial species utilize surface appendages called type IV pili (T4P) to interact with their environment. These structures are dynamically extended and retracted from the cell surface, which is critical for diverse functions. Some…
View article: Integrative Structure and Function of the <i>Vibrio cholerae</i> Competence Pilus Machine
Integrative Structure and Function of the <i>Vibrio cholerae</i> Competence Pilus Machine Open
Type IV pili are hair-like, surface-exposed polymers involved in many fundamental biological processes. The competence pilus (CP) is responsible for natural transformation, the ability to acquire exogenous DNA. Here we purified the Vibrio …
View article: Using Machine Learning to Analyze Molecular Dynamics Simulations of Biomolecules
Using Machine Learning to Analyze Molecular Dynamics Simulations of Biomolecules Open
Machine learning (ML) techniques have become powerful tools in both industrial and academic settings. Their ability to facilitate analysis of complex data and generation of predictive insights is transforming how scientific problems are ap…
View article: Machine Learning of Molecular Dynamics Simulations Provides Insights into the Modulation of Viral Capsid Assembly
Machine Learning of Molecular Dynamics Simulations Provides Insights into the Modulation of Viral Capsid Assembly Open
An effective approach in the development of novel antivirals is to target the assembly of viral capsids by using capsid assembly modulators (CAMs). CAMs targeting hepatitis B virus (HBV) have two major modes of function: they can either ac…
View article: Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly
Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly Open
Molecular dynamics (MD) simulations provide a detailed description of biophysical processes allowing mechanistic questions to be addressed at the atomic level. The promise of such approaches is partly hampered by well known sampling issues…
View article: Recent Advances in Membrane Protein Simulations
Recent Advances in Membrane Protein Simulations Open
View article: DeepPath: Overcoming data scarcity for protein transition pathway prediction using physics-based deep learning
DeepPath: Overcoming data scarcity for protein transition pathway prediction using physics-based deep learning Open
The structural dynamics of proteins play a crucial role in their function, yet most experimental and deep learning methods produce only static models. While molecular dynamics (MD) simulations provide atomistic insight into conformational …
View article: Probing the Dynamics of Yersinia Adhesin A (YadA) in Outer Membranes Hints at Requirements for β-Barrel Membrane Insertion
Probing the Dynamics of Yersinia Adhesin A (YadA) in Outer Membranes Hints at Requirements for β-Barrel Membrane Insertion Open
The vast majority of cells are protected and functionalized by a dense surface layer of glycans, proteoglycans, and glycolipids. This surface represents an underexplored space in structural biology that is exceedingly challenging to recrea…
View article: Conserved lipid-facing basic residues promote the insertion of the porin OmpC into the <i>E. coli</i> outer membrane
Conserved lipid-facing basic residues promote the insertion of the porin OmpC into the <i>E. coli</i> outer membrane Open
Almost all integral membrane proteins that reside in the outer membrane (OM) of gram-negative bacteria contain a closed amphipathic β sheet (“β barrel”) that serves as a membrane anchor. The membrane integration of β barrel structures is c…
View article: Machine learning of molecular dynamics simulations provides insights into modulation of viral capsid assembly
Machine learning of molecular dynamics simulations provides insights into modulation of viral capsid assembly Open
An effective approach in the development of novel antivirals is to target the assembly of viral capsids using capsid assembly modulators (CAMs). CAMs targeting hepatitis B virus (HBV) have two major modes of function: they can either accel…
View article: Protein Structure Prediction in the 3D HP Model Using Deep Reinforcement Learning
Protein Structure Prediction in the 3D HP Model Using Deep Reinforcement Learning Open
We address protein structure prediction in the 3D Hydrophobic-Polar lattice model through two novel deep learning architectures. For proteins under 36 residues, our hybrid reservoir-based model combines fixed random projections with traina…
View article: Mg2+-dependent mechanism of environmental versatility in a multidrug efflux pump
Mg2+-dependent mechanism of environmental versatility in a multidrug efflux pump Open
Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are major drivers of multidrug resistance among gram-negative bacteria. Cations, such as Mg2+, become concentrated within the perip…
View article: Protein Structure Prediction in the 3D HP Model Using Deep Reinforcement Learning
Protein Structure Prediction in the 3D HP Model Using Deep Reinforcement Learning Open
We address protein structure prediction in the 3D Hydrophobic-Polar lattice model through two novel deep learning architectures. For proteins under 36 residues, our hybrid reservoir-based model combines fixed random projections with traina…
View article: The influence of downstream structured elements within mRNA on the dynamics of intersubunit rotation in ribosomes
The influence of downstream structured elements within mRNA on the dynamics of intersubunit rotation in ribosomes Open
Proper codon/anti-codon pairing within the ribosome necessitates linearity of the transcript. Any structures formed within a messenger RNA (mRNA) must be unwound before the respective codon is interpreted. Linearity, however, is not always…
View article: Structural characterization of the POTRA domains from A. baumannii reveals new conformations in BamA
Structural characterization of the POTRA domains from A. baumannii reveals new conformations in BamA Open
View article: Allosteric coupling of substrate binding and proton translocation in MmpL3 transporter from <i>Mycobacterium tuberculosis</i>
Allosteric coupling of substrate binding and proton translocation in MmpL3 transporter from <i>Mycobacterium tuberculosis</i> Open
Infections caused by Mycobacterium spp. are very challenging to treat, and multidrug-resistant strains rapidly spread in human populations. Major contributing factors include the unique physiological features of these bacteria, drug efflux…
View article: Molecular Dynamics Reveals Altered Interactions between Belzutifan and HIF-2 with Natural Variant G323E or Proximal Phosphorylation at T324
Molecular Dynamics Reveals Altered Interactions between Belzutifan and HIF-2 with Natural Variant G323E or Proximal Phosphorylation at T324 Open
In patients with von-Hippel Lindau (VHL) disease, hypoxia-independent accumulation of HIF-2α leads to increased transcriptional activity of HIF-2α:ARNT that drives cancers such as renal cell carcinoma. Belzutifan, a recently FDA-approved d…
View article: Broadening access to small-molecule parameterization with the force field toolkit
Broadening access to small-molecule parameterization with the force field toolkit Open
Access to accurate force-field parameters for small molecules is crucial for computational studies of their interactions with proteins. Although a number of general force fields for small molecules exist, e.g., CGenFF, GAFF, and OPLS, they…
View article: Mg<sup>2+</sup>-dependent mechanism of environmental versatility in a multidrug efflux pump
Mg<sup>2+</sup>-dependent mechanism of environmental versatility in a multidrug efflux pump Open
Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are a major driver of multidrug resistance among Gram-negative bacteria. The periplasm provides a distinct environment between the inner and o…
View article: SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii
SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii Open
View article: Thicket and Mesh: How the Outer Membrane Can Resist Tension Imposed by the Cell Wall
Thicket and Mesh: How the Outer Membrane Can Resist Tension Imposed by the Cell Wall Open
The cell envelope of Gram-negative bacteria is composed of an outer membrane (OM) and an inner membrane (IM) and a peptidoglycan cell wall (CW) between them. Combined with Braun's lipoprotein (Lpp), which connects the OM and the CW, and nu…
View article: Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile
Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile Open
SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding in proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation charact…
View article: Biophysics-Guided Lead Discovery of HBV Capsid Assembly Modifiers
Biophysics-Guided Lead Discovery of HBV Capsid Assembly Modifiers Open
Hepatitis B virus (HBV) is the leading cause of chronic liver pathologies worldwide. HBV nucleocapsid, a key structural component, is formed through the self-assembly of the capsid protein units. Therefore, interfering with the self-assemb…
View article: Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10
Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10 Open
Doa10 (MARCHF6 in metazoans) is a large polytopic membrane-embedded E3 ubiquitin ligase in the endoplasmic reticulum (ER) that plays an important role in quality control of cytosolic and ER proteins. Although Doa10 is highly conserved acro…
View article: Generative β-hairpin design using a residue-based physicochemical property landscape
Generative β-hairpin design using a residue-based physicochemical property landscape Open
View article: Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10
Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10 Open
Doa10 (MARCH6 in metazoans) is a large polytopic membrane-embedded E3 ubiquitin ligase in the endoplasmic reticulum (ER) that plays an important role in quality control of cytosolic and ER proteins. Although Doa10 is highly conserved acros…
View article: Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller
Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller Open
View article: From simple to complex: Reconstructing all-atom structures from coarse-grained models using cg2all
From simple to complex: Reconstructing all-atom structures from coarse-grained models using cg2all Open