A5044296777- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- T-cell and B-cell Immunology
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Neurotransmitter Receptor Influence on Behavior
- Advanced NMR Techniques and Applications
- Theoretical and Computational Physics
- Mass Spectrometry Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Molecular Sensors and Ion Detection
- Cellular transport and secretion
- Gene expression and cancer classification
- Polyoxometalates: Synthesis and Applications
- Topological and Geometric Data Analysis
- Markov Chains and Monte Carlo Methods
- Adenosine and Purinergic Signaling
- Stochastic processes and statistical mechanics
Cornell University
2009-2025
Freie Universität Berlin
2015-2023
Institute of Molecular Biology
2018
ModeHunter is a modular Python software package for the simulation of 3D biophysical motion across spatial resolution scales using modal analysis elastic networks. It has been curated from our in-house scripts over last 15 years, with focus on detecting similarities between atomic structures, coarse-grained graphs, and volumetric data obtained or biomedical imaging origins, such as electron microscopy tomography. With ModeHunter, normal modes can be analyzed various static visualization...
Neurotransmitter:sodium symporters (NSSs) play a critical role in signaling by reuptake of neurotransmitters. Eukaryotic NSSs are chloride-dependent, whereas prokaryotic NSS homologs like LeuT chloride-independent but contain an acidic residue (Glu290 LeuT) at site where eukaryotic have serine. The LeuT-E290S mutant displays chloride-dependent activity. We show that, cocrystallized with bromide or chloride, the anion is coordinated side chain hydroxyls from Tyr47, Ser290, and Thr254 amide...
Abstract Presentation of antigenic peptides by major histocompatibility complex class II (MHC-II) proteins determines T helper cell reactivity. The MHC-II genetic locus displays a large degree allelic polymorphism influencing the peptide repertoire presented resulting protein allotypes. During antigen processing, human leukocyte (HLA) molecule HLA-DM (DM) encounters these distinct allotypes and catalyzes exchange placeholder CLIP exploiting dynamic features MHC-II. Here, we investigate 12...
Neurotransmitter:sodium symporters (NSSs) terminate neurotransmission by Na(+)-dependent reuptake of released neurotransmitters. Previous studies suggested that Na(+)-binding reconfigures dynamically coupled structural elements in an allosteric interaction network (AIN) responsible for function-related conformational changes, but the intramolecular pathway this mechanism has remained uncharted. We describe a new approach modeling and analysis dynamics bacterial NSS homolog LeuT. From...
Abstract The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics antigen exchange remain elusive. By combining NMR-detected H/D with Markov modelling analysis an aggregate 275 microseconds molecular simulations, we reveal that stable pMHCII spontaneously samples intermediate conformations relevant peptide exchange. More specifically, observe two major pathways: kinetic stability...
Excitatory amino acid transporters (EAATs) are membrane proteins responsible for reuptake of glutamate from the synaptic cleft to terminate neurotransmission and help prevent neurotoxically high, extracellular concentrations. Important structural information about these emerged crystal structures GltPh, a bacterial homologue EAATs, in conformations facing outward inward. These remarkably different considered be end points substrate translocation path (STP), suggesting that transport...
Neurotransmitter:sodium symporters (NSSs) mediate reuptake of neurotransmitters from the synaptic cleft and are targets for several therapeutics psychostimulants. The prokaryotic NSS homologue, LeuT, represents a principal structural model Na(+)-coupled transport catalyzed by these proteins. Here, we used site-directed fluorescence quenching spectroscopy to identify in LeuT substrate-induced conformational rearrangement at inner gate conceivably leading formation intermediate preceding...
Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low abuse liability and prefer less conformations. Here, we use spectrum of computational modeling simulation approaches to obtain underlying molecular mechanism atomistic detail. Interestingly, our quantum mechanical calculations dynamics (MD) simulations suggest that derivative JHW007 prefers...
Phospholipase C (PLC) β2, a well studied member of the family enzymes that catalyze hydrolysis membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) into secondary messengers, can be activated by Gβγ subunits heterotrimeric G-proteins in manner depends on presence and composition associated phospholipid surface. The N-terminal pleckstrin homology (PH) domain PLCβ2 mediates both response to binding, but how these interactions are coupled yield an catalytic core remains...
Chromatic polynomials and related graph invariants are central objects in both theory statistical physics. Computational difficulties, however, have so far restricted studies of such to graphs that were either very small, sparse or highly structured. Recent algorithmic advances (Timme et al 2009 New J. Phys. 11 023001) now make it possible compute chromatic for moderately sized arbitrary structure number edges. Here we present ensembles random with up 30 vertices, over the entire range edge...
Counting problems, determining the number of possible states a large system under certain constraints, play an important role in many areas science. They naturally arise for complex disordered systems physics and chemistry, mathematical graph theory, computer however, are among hardest problems to access computationally. Here, we suggest novel method benchmark counting problem, finding chromatic polynomials graphs. We develop vertex-oriented symbolic pattern matching algorithm that exploits...
Many modeling analyses of molecular dynamics (MD) simulations are based on a definition states that can be (groups of) clusters simulation frames in feature space composed coordinates. With increasing dimension this (due to the size or complexity simulated molecule), it becomes very difficult cluster underlying MD data and estimate statistically robust model. To mitigate "curse dimensionality", one reduce space, e.g., with principal component time-lagged independent analysis transformations,...