Dr. David Reha

The channel Orai1 requires Ca²⁺ store depletion in the endoplasmic reticulum and an interaction with the Ca²⁺ sensor STIM1 to mediate Ca²⁺ signaling. Alterations in Orai1-mediated Ca²⁺ influx have been linked to several pathological conditions including immunodeficiency, tubular myopathy, and cancer. We screened large-scale cancer genomics data sets for dysfunctional Orai1 mutants. Five of the identified Orai1 mutations resulted in constitutively active gating and transcriptional activation. Our analysis showed that certain Orai1 mutations were clustered in the transmembrane 2 helix surrounding the pore, which is a trigger site for Orai1 channel gating. Analysis of the constitutively open Orai1 mutant channels revealed two fundamental gates that enabled Ca²⁺ influx: Arginine side chains were displaced so they no longer blocked the pore, and a chain of water molecules formed in the hydrophobic pore region. Together, these results enabled us to identify a cluster of Orai1 mutations that trigger Ca²⁺ permeation associated with gene transcription and provide a gating mechanism for Orai1.

23 December 2016 in RSC Advances

Journal Article

Theoretical and experimental study of the antifreeze protein AFP752, trehalose and dimethyl sulfoxide cryoprotection mechanism: correlation with cryopreserved cell viability

Martin Golan

Jan Richter

DŠ

In this work the physico-chemical properties of selected cryoprotectants (antifreeze protein TrxA-AFP752, trehalose and dimethyl sulfoxide) were correlated with their impact on the constitution of ice and influence on frozen/thawed cell viability. The freezing processes and states of investigated materials solutions were described and explained from a fundamental point of view using ab initio modelling (molecular dynamics, DFT), Raman spectroscopy, differential scanning calorimetry and X-ray diffraction. For the first time, in this work we correlated the microscopic view (modelling) with the description of the frozen solution states and put these results in the context of human skin fibroblast viability after freezing and thawing. DMSO and AFP had different impacts on their solution's freezing process but in both cases the ice crystallinity size was considerably reduced. DMSO and AFP treatment in different ways improved the viability of frozen/thawed cells.

1 March 2006 in The Journal of Physical Chemistry B

Journal Article

Structure of Isolated Tryptophyl-Glycine Dipeptide and Tryptophyl-Glycyl-Glycine Tripeptide: Ab Initio SCC-DFTB-D Molecular Dynamics Simulations and High-Level Correlated ab Initio Quantum Chemical Calculations

Haydee Valdés

David Reha

Pavel Hobza

About Me

Dr. David Řeha Head of the Laboratory of Structural Biology and Bioinformatics, Institute of Microbiology of the Czech Academy of Sciences; Zamek 136, Nove Hrady, Czech Republic Education: 2005 PhD in Physical Chemistry, Charles University in Prague, Czech Republic Work experience: 2007-2099 Postdoc, University of Leeds, UK 2009-2011 Postdoc, University of Essex, Colchester, UK 2011-2016 PI, Global Change Research Institute of the CAS, Nove Hrady, Czech Republic 2016-now PI, Institute of Microbiology of the CAS, Nove Hrady, Czech Republic Research interest: The modeling of biomolecular systems and the study of intermolecular interactions using computational methods including molecular dynamics (MD) simulations, quantum mechanics/molecular mechanics (QM/MM) calculations, and molecular docking. Current research projects are focused on studying the functional properties of DNA and a wide range of proteins including membrane proteins; the study of mechanisms of enzymatic reactions and modelling their transition states; the study of charge transfer in DNA, photosynthetic proteins, and redox proteins. Development of the new methods and their implementation for computational studies of biomolecules.

Dr. David Reha

Dr. David Reha

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