Harel Weinstein, DSc
img_Harel Weinstein
ADJUNCT PROFESSOR | Pharmacological Sciences
Molecular Biophysics of Specificity and Signal Transduction in the Function of Proteins and DNA

Click \r\nHERE for details of recent work

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\r\nMy laboratory aims to discover the structure, dynamic and electronic determinants of biological processes underlying physiological functions, through the development and application of methods in theoretical and computational biophysics. We seek a mechanistic understanding at the molecular level of detail, anchored in experimental information about structures and properties of cellular components and physiological mechanisms. Our approaches include theoretical determinations of molecular structure and properties, and computational simulations of molecular mechanisms and processes that can be studied with great accuracy.\r\n

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The theoretical studies are designed to complement experimentation in providing mechanistic insights about systems of ever increasing size and complexity, and to guide pointed experimental exploration of cellular processes and functions in numerous collaborative studies. The theoretical methods we use are continuously being refined and tested in the study of biomolecular systems. They are based on methods of quantum and statistical mechanics, and implemented in novel algorithms running on supercomputers and various computational graphics machines.\r\n\r\n\r\n

A unifying theme is the understanding of mechanisms triggered by molecular recognition and leading to signal transduction. We study structural specificity and dynamics in three main areas in which such processes determine physiological mechanisms:\r\n\r\n\r\n

  • The study of specificity and functional trigger produced by protein binding to DNA in the regulation of gene expression, based on the structural dynamics of DNA, protein-binding properties of DNA and the structural and functional consequences of the interactions. Current work focusses on structural and dynamic determinants for the specificity and function of TATA-box binding proteins, zinc fingers, and the tumor suppressor p53. \r\n
  • Exploration of the structural context for the determinants of specificity in mechanisms of cellular signaling through ligand recognition and receptor response. Current work examines molecular structure and signal transduction mechanisms in transmembrane G-protein coupled receptors; and especially \r\n\r\n
  • receptors for the neurotransmitter serotonin: 5-HT1A, 5-HT2A and 5-HT2C; \r\n
  • ligand action and receptor structure for gonadotropin releasing hormone - GnRH, and of m,k,d-opioid receptors; \r\n
  • structure-function relations in the mechanisms of chemokine receptors as co-receptors for HIV infectivity. \r\n\r\n
  • The molecular mechanisms responsible for recognition, decoding and processing of Ca2+ signals through the EF-hand Ca-binding proteins. Ongoing work examines the structure, dynamics, function and protein engineering of Calmodulin, cardiac and skeletal TroponinC, and CalbindinD9k \r\n
  • The structural basis of molecular mechanisms in the recognition and modulation of protein-protein interactions in the signal transduction cascade. Current work is on the function of the Gbg subunit of the heterotrimeric G proteins and its modulation by peptides from various effectors. Practical considerations include structure-based design of specific "signal breaker" ligands affecting kinase and cyclase effector systems. \r\n\r\n
  • BS, Technion-Israel Institute of Technology

    MS, Technion-Israel Institute of Technology

    DS, Technion-Israel Institute of Technology