A5085406263- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- Computer Graphics and Visualization Techniques
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- Mass Spectrometry Techniques and Applications
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Receptor Mechanisms and Signaling
- Scientific Computing and Data Management
- Gene Regulatory Network Analysis
- Atmospheric chemistry and aerosols
- Computational Drug Discovery Methods
- Neuroscience and Neural Engineering
- Gene expression and cancer classification
- Computational Geometry and Mesh Generation
- 3D Printing in Biomedical Research
University of California, San Diego
2014-2025
National Institute on Aging
2021-2025
Jacobs (United States)
2021-2024
Scripps Institution of Oceanography
2024
The University of Texas Health Science Center at San Antonio
2022
Vital Strategies
2022
National Institutes of Health
2015-2021
Institute on Aging
2021
Massachusetts Institute of Technology
2017
Harvard–MIT Division of Health Sciences and Technology
2017
Predicting the rate of nonfacilitated permeation solutes across lipid bilayers is important to drug design, toxicology, and signaling. These rates can be estimated using molecular dynamics simulations combined with inhomogeneous solubility-diffusion model, which requires calculation potential mean force position-dependent diffusivity solute along transmembrane axis. In this paper, we assess efficiency accuracy several methods for permeability a model DMPC bilayer urea, benzoic acid, codeine....
Automated classification of human anatomy is an important prerequisite for many computer-aided diagnosis systems. The spatial complexity and variability throughout the body makes difficult. "Deep learning" methods such as convolutional networks (ConvNets) outperform other state-of-the-art in image tasks. In this work, we present a method organ- or body-part-specific anatomical medical images acquired using computed tomography (CT) with ConvNets. We train ConvNet, 4,298 separate axial 2D...
Owing to recent developments in computational algorithms and architectures, it is now computationally tractable explore biologically relevant, equilibrium dynamics of realistically-sized functional proteins using all-atom molecular simulations. Molecular simulations coupled with Markov state models a nascent but rapidly growing technology that enabling robust exploration dynamics. The objective this work the challenges coupling study proteins. Using studies as framework, we progress...
Abstract Cristae are high‐curvature structures in the inner mitochondrial membrane (IMM) that crucial for ATP production. While cristae‐shaping proteins have been defined, analogous lipid‐based mechanisms yet to be elucidated. Here, we combine experimental lipidome dissection with multi‐scale modeling investigate how lipid interactions dictate IMM morphology and generation. When modulating phospholipid (PL) saturation engineered yeast strains, observed a surprisingly abrupt breakpoint...
We revisit the origin of Larson's scaling laws describing structure and kinematics molecular clouds. Our analysis is based on recent observational measurements data from a suite six simulations interstellar medium, including effects self-gravity, turbulence, magnetic field, multiphase thermodynamics. Simulations isothermal supersonic turbulence reproduce observed slopes in linewidth-size mass-size relations. Whether or not self-gravity included, relation remains same. The relation, instead,...
Recent advances in electron microscopy have enabled the imaging of single cells 3D at nanometer length scale resolutions. An uncharted frontier for silico biology is ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing micrograph images into volume meshes, which can then form basis computer numerical techniques as Finite Element Method. In this paper, we describe use our recently rewritten mesh processing software,...
Membrane curvature is essential to diverse cellular functions. While classically attributed structured domains, recent work illustrates that intrinsically disordered proteins are also potent drivers of membrane bending. Specifically, repulsive interactions among domains drive convex bending, while attractive concave creating membrane-bound, liquid-like condensates. How might contain both and affect curvature? Here, we examined chimeras combined interactions. When the domain was closer...
Prediction of passive permeation rates solutes across lipid bilayers is important to drug design, toxicology, and other biological processes such as signaling. The inhomogeneous solubility-diffusion (ISD) equation traditionally used relate the position-dependent potential mean force diffusivity permeability coefficient. ISD derived via Smoluchowski assumes overdamped system dynamics. It has been suggested that complex membrane environment may exhibit more complicated damping conditions. Here...
Variable wind speeds over the ocean can have a significant impact on formation mechanism and physical-chemical properties of sea spray aerosols (SSA), which in turn influence their climate-relevant impacts. Herein, for first time, we investigate effects speed size-dependent morphology composition individual nascent SSA generated from wind-wave interactions natural seawater within channel as function size particle-to-particle variability. Filter-based thermal optical analysis, atomic force...
Abstract Axons are ultrathin membrane cables that specialized for the conduction of action potentials. Although their diameter is variable along length, how morphology determined unclear. Here, we demonstrate unmyelinated axons mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in repeatedly length interspersed with a thin cable ~60 like pearls-on-a-string. In silico modeling suggests this axon nanopearling can be explained by mechanical properties. Treatments...
Abstract Undergraduate biochemistry laboratory courses often do not provide students with an authentic research experience, particularly when the express purpose of is purely instructional. However, instructional course that inquiry‐ and research‐based could simultaneously impart scientific knowledge foster a student's expertise confidence. We have developed year‐long undergraduate curriculum wherein determine, via experiment computation, function protein known three‐dimensional structure....
Efficient prediction and ranking of small molecule binders by their kinetic (kon koff) thermodynamic (ΔG) properties can be a valuable metric for drug lead optimization, as these quantities are often indicators in vivo efficacy. We have previously described hybrid molecular dynamics, Brownian milestoning model, Simulation Enabled Estimation Kinetic Rates (SEEKR), that predict kon's, koff's, ΔG's. Here we demonstrate the effectiveness this approach series seven compounds model system,...
Advances in imaging methods such as electron microscopy, tomography, and other modalities are enabling high-resolution reconstructions of cellular organelle geometries. Such advances pave the way for using these geometries biophysical mathematical modeling once data can be represented a geometric mesh, which, when carefully conditioned, enables discretization solution partial differential equations. In this work, we outline steps naïve user to approach Geometry-preserving Adaptive MeshER...
Dendritic spines act as biochemical computational units and must adapt their responses according to activation history. Calcium influx acts the first signaling step during postsynaptic is a determinant of synaptic weight change. also come in variety sizes shapes. To probe relationship between calcium dynamics spine morphology, we used stochastic reaction-diffusion model idealized realistic geometries. We show that despite nature various channels, receptors, pumps, size shape can modulate...
Organelles such as mitochondria have characteristic shapes that are critical to their function. Recent efforts revealed the curvature contributions of individual lipid species can be a factor in generation membrane shape these organelles. Inspired by lipidomics data from yeast mitochondrial membranes, we used Martini coarse-grained molecular dynamics simulations investigate how composition facilitates shaping. We found increasing saturation increases bending rigidity while reducing monolayer...