A5088083389- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- DNA and Nucleic Acid Chemistry
- Cellular transport and secretion
- Force Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Biochemical and Structural Characterization
- Hemoglobin structure and function
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Mass Spectrometry Techniques and Applications
- Influenza Virus Research Studies
- Bacterial Genetics and Biotechnology
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Photoreceptor and optogenetics research
- Advanced NMR Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- Copper Interconnects and Reliability
- Erythrocyte Function and Pathophysiology
- Protein purification and stability
- Origins and Evolution of Life
Max Delbrück Center
2016-2023
Electric Ant Lab (Netherlands)
2021
Fritz Haber Institute of the Max Planck Society
2016-2021
Northeastern University
2019
Rice University
2012-2017
Center for Theoretical Biological Physics
2008-2017
University of California, San Diego
2010-2012
University of Missouri
2012
UC San Diego Health System
2009
University of California, Los Angeles
1972-1973
Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding both long scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our short high energetic structural resolution. Thus, atomic details included be used bridge between these two approaches. We report robustness mechanisms in one such all-atom model. Results for B domain A,...
Molecular dynamics simulations with coarse-grained and/or simplified Hamiltonians are an effective means of capturing the functionally important long-time and large-length scale motions proteins RNAs. Structure-based Hamiltonians, models developed from energy landscape theory protein folding, have become a standard tool for investigating biomolecular dynamics. SMOG@ctbp is effort to simplify use structure-based models. The purpose web server two fold. First, simplifies process implementing...
Molecular dynamics simulations with coarse-grained or simplified Hamiltonians have proven to be an effective means of capturing the functionally important long-time and large-length scale motions proteins RNAs. Originally developed in context protein folding, structure-based models (SBMs) since been extended probe a diverse range biomolecular processes, spanning from RNA folding functional transitions molecular machines. The hallmark feature model is that part, all, potential energy function...
Structure-based models (SBMs) are simplified of the biomolecular dynamics that arise from funneled energy landscapes. We recently introduced an all-atom SBM explicitly represents atomic geometry a biomolecule. While this initial study showed robustness Hamiltonian to changes in many energetic parameters, important aspect, which has not been explored previously, is definition native interactions. In study, we propose general for generating atomically grained contact maps called "Shadow". The...
Membrane remodeling and repair are essential for all cells. Proteins that perform these functions include Vipp1/IM30 in photosynthetic plastids, PspA bacteria, ESCRT-III eukaryotes. Here, using a combination of evolutionary structural analyses, we show protein families homologous share common ancient origin likely predates the last universal ancestor. This homology is evident cryo-electron microscopy structures Vipp1 rings from cyanobacterium Nostoc punctiforme presented over range...
Protein knots and slipknots, mostly regarded as intriguing oddities, are gradually being recognized significant structural motifs. Recent experimental results show that knotting, starting from a fully extended polypeptide, has not yet been observed. Understanding the nucleation process of folding is thus natural challenge for both theoretical investigation. In this study, we employ energy landscape theory molecular dynamics to elucidate entire mechanism. The full free knotted protein mapped...
Recent experiments have conclusively shown that proteins are able to fold from an unknotted, denatured polypeptide the knotted, native state without aid of chaperones. These consistent with a growing body theoretical work showing funneled, minimally frustrated energy landscape is sufficient small complex topologies. Here, we present investigation folding knotted protein, 2ouf, engineered in laboratory by domain fusion mimics evolutionary pathway for proteins. Unlike previously studied...
Experiments demonstrate that Mg(2+) is crucial for structure and function of RNA systems, yet the detailed molecular mechanism action on not well understood. We investigate interplay between at atomic resolution through ten 2-μs explicit solvent dynamics simulations SAM-I riboswitch with varying ion concentrations. The structure, including three stemloops, very stable this time scale. Simulations reveal outer-sphere coordinated ions fluctuate same scale as RNA, their couple. Locally,...
RNA is highly sensitive to the ionic environment and typically requires ${\mathrm{Mg}}^{2+}$ form compact structures. There a need for models capable of describing ion atmosphere surrounding with quantitative accuracy. We present model electrostatics apply it within coarse-grained molecular dynamics simulation. The treats ions explicitly account ion-ion correlations neglected by mean-field theories. Since theories capture KCl well, treated implicitly generalized Manning counterion...
Abstract It has long been recognized that the thermodynamics of mRNA–tRNA base pairing is insufficient to explain high fidelity and efficiency aminoacyl-tRNA (aa-tRNA) selection by ribosome. To rationalize this apparent inconsistency, Hopfield proposed ribosome may improve accuracy utilizing a multi-step kinetic proofreading mechanism. While biochemical, structural single-molecule studies have provided detailed characterization aa-tRNA selection, there limited understanding how...
Recently, experiments have confirmed that trefoil knotted proteins can fold spontaneously, consistent with predictions from simulations of simplified protein models. These suggest folding the knot involves threading terminal across a twisted loop via slipknot configuration. Here, we report unbiased all-atom explicit-solvent knotting dynamics protein. In totaling 40 μs, find 5 out 15 reach native state when initiated unknotted, slipknotted intermediates. The completed events had durations...
Significance Influenza hemagglutinin (HA), a viral surface glycoprotein, undergoes critical and large conformational rearrangement to promote fusion of the membrane with host membrane. Unlike variable receptor binding domain HA 1 , coiled-coil 2 is highly conserved, making promising target for therapeutics. Furthermore, structural similarity between influenza other proteins, including that HIV, makes valuable model system. We build using information from only prefusion postfusion...
RfaH is a virulence factor from Escherichia coli whose C-terminal domain (CTD) undergoes dramatic α-to-β conformational transformation. The CTD in its α-helical fold stabilized by interactions with the N-terminal (NTD), masking an RNA polymerase binding site until specific recruitment encountered. Domain dissociation triggered upon to DNA, allowing NTD interact facilitate transcription while refolds into β-barrel conformation that interacts ribosome activate translation. However, structural...
Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form highly curved neck regions of and thought to function as selective entry gates into space. Little is known about how CJs generated maintained. We show that central coiled-coil (CC) domain mitochondrial contact site organizing system subunit Mic60 forms an elongated, bow tie–shaped tetrameric assembly. Mic19 promotes tetramerization via a conserved interface between mitofilin CHCH...
A four-helix bundle is a well-characterized motif often used as target for designed pharmaceutical therapeutics and nutritional supplements. Recently, we discovered new structural complexity within this created by disulphide bridge in the long-chain helical cytokine leptin. When oxidized, leptin contains creating covalent-loop through which part of polypeptide chain threaded (as seen knotted proteins). We explored whether other proteins contain similar intriguing knot-like structure 11...
Evolution has selected a protein's sequence to be consistent with the native state geometry, as this configuration must both thermodynamically stable and kinetically accessible prevent misfolding loss of function. In simple protein geometries, such coiled-coil helical bundles, symmetry produces competing, globally different, near mirror image identical secondary structure similar contact interactions. Experimental techniques circular dichroism, which rely on probing content, cannot readily...
Abstract Dynamin-like proteins (DLPs) are large GTPases that restructure membrane. DLPs such as the mitofusins form heterotypic oligomers between isoform pairs bridge and fuse opposing membranes. In bacteria, oligomerisation may also be important for membrane remodelling most DLP genes paired within operons. How tether membranes is unknown. Here we show crystal structure of a pair from pathogen Campylobacter jejuni . A 2:2 stoichiometric tetramer observed where heterodimers, conjoined by...
Applying simulations with structure-based