A5061232477- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- Machine Learning in Materials Science
- Photosynthetic Processes and Mechanisms
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Spectroscopy and Quantum Chemical Studies
- Lipid Membrane Structure and Behavior
- Spectroscopy and Laser Applications
- Electron and X-Ray Spectroscopy Techniques
- ATP Synthase and ATPases Research
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Scientific Research and Discoveries
- Force Microscopy Techniques and Applications
- RNA modifications and cancer
- Advanced Chemical Physics Studies
- Antibiotics Pharmacokinetics and Efficacy
- Mitochondrial Function and Pathology
- Algorithms and Data Compression
- Photoreceptor and optogenetics research
- Genomics and Chromatin Dynamics
- Optical Systems and Laser Technology
- Microbial Metabolic Engineering and Bioproduction
- Bacterial Genetics and Biotechnology
Arizona State University
2019-2024
Tempe Union High School District
2023
Eastern Washington University
2020-2023
We observe previously unknown interactions between clinically important adenovirus vector capsids, platelet factor 4, and CAR.
Despite significant advances in resolution, the potential for cryo-electron microscopy (EM) to be used determining structures of protein–drug complexes remains unrealized. Determination accurate and coordination bound ligands necessitates simultaneous fitting models into density envelopes, exhaustive sampling ligand geometries, and, most importantly, concomitant rearrangements side chains optimize binding energy changes. In this article, we present a flexible-fitting pipeline where molecular...
Cryo-electron microscopy (cryo-EM) has produced a number of structural models the SARS-CoV-2 spike, already prompting biomedical outcomes. However, these reported and their associated electrostatic potential maps represent an unknown admixture conformations stemming from underlying energy landscape spike protein. As with any protein, some spike's conformational motions are expected to be biophysically relevant, but cannot interpreted only by static models. Using experimental cryo-EM images,...
Driving molecular dynamics simulations with data-guided collective variables offer a promising strategy to recover thermodynamic information from structure-centric experiments. Here, the three-dimensional electron density of protein, as it would be determined by cryo-EM or x-ray crystallography, is used achieve simultaneously free-energy costs conformational transitions and refined atomic structures. Unlike previous density-driven methodologies that determine only best map-model fits, our...
Abstract Adenovirus derived vectors, based on chimpanzee adenovirus Y25 (ChAdOx1) and human type 26 are proving critical in combatting the 2019 SARS-CoV-2 pandemic. Following emergency use authorisation, scale up vaccine administration has inevitably revealed related adverse effects; too rare to observe even large Phase-III clinical trials. These include vaccine-induced thrombotic thrombocytopenia (VITT), an ultra-rare event which patients develop life-threatening blood clots 5-24 days...
Recent advances in cryo-electron microscopy (cryo-EM) have enabled modeling macromolecular complexes that are essential components of the cellular machinery. The density maps derived from cryo-EM experiments often integrated with manual, knowledge-driven or artificial intelligence-driven and physics-guided computational methods to build, fit, refine molecular structures. Going beyond a single stationary-structure determination scheme, it is becoming more common interpret experimental data an...
Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions their contributions to heterochromatin functions remain elusive. Here, we present cryoelectron microscopy (cryo-EM) structure of an HP1α dimer bound H2A.Z-nucleosome, revealing two distinct HP1α-nucleosome interfaces. The primary binding site is located at N terminus histone H3, specifically trimethylated lysine 9...
SUMMARY Glucose, the primary cellular energy source, is metabolized through glycolysis initiated by rate-limiting enzyme Hexokinase (HK). In energy-demanding tissues like brain, HK1 dominant isoform, primarily localized on mitochondria, crucial for efficient glycolysis-oxidative phosphorylation coupling and optimal generation. This study unveils a unique mechanism regulating activity, glycolysis, dynamics of mitochondrial coupling, mediated metabolic sensor O-GlcNAc transferase (OGT). OGT...
We report the first 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from purple bacterium, which reveals cascade energy-conversionsteps culminating into generation ATP sunlight. Molecular dynamics simulations ofthis elucidate how integral-membrane complexes influences local curvature as ployto tune photoexcitation pigments. Brownian small-molecules within probe mechanisms directional charge transport under various pH and salinity conditions....
Cryo-electron microscopy (EM) requires molecular modeling to refine structural details from data. Ensemble models arrive at low free-energy structures, but are computation- ally expensive and limited resolving only small proteins that cannot be resolved by cryo-EM. Here, we introduce CryoFold - a pipeline of dynamics simulations deter- mines ensembles protein structures directly sequence integrating density data varying sparsity 3–5 A ̊ resolution with coarse-grained topological knowledge...
Abstract In this paper, we develop a formulation to utilize reinforcement learning and sampling-based robotics planning derive low free energy transition pathways between two known states. Our uses Jarzynski’s equality the stiffspring approximation obtain point estimates of energy, construct an informed path search with atomistic resolution. At core framework, is our first ever attempt use policy driven adaptive steered molecular dynamics (SMD) control simulations. We show that both...
Abstract Driving molecular dynamics simulations with data-guided collective variables offer a promising strategy to recover thermodynamic information from structure-centric experiments. Here, the 3-dimensional electron density of protein, as it would be determined by cryo-EM or X-ray crystallography, is used achieve simultaneously free-energy costs conformational transitions and refined atomic structures. Unlike previous density-driven methodologies that determine only best map-model fits,...
Abstract Molecular dynamics (MD) simulations have emerged to become the back-bone of today’s computational biophysics. Simulation tools such as, NAMD, AMBER and GROMACS accumulated more than 100,000 users. Despite this remarkable success, now also bolstered by compatibility with graphics processor units (GPUs) exascale computers, even most scalable cannot access biologically relevant timescales - number numerical integration steps necessary for solving differential equations in a...
Cryo-EM is a powerful method for determining protein structures. But it requires computational assistance. Physics-based computations have the power to give low-free-energy structures and ensembles of populations, but been computationally limited only small soluble proteins. Here, we introduce CryoFold. By integrating data varying sparsity from electron density maps 3–5 Å resolution with coarse-grained physical knowledge secondary tertiary interactions, CryoFold determines directly sequence....