Grupa badawcza dr hab. Doroty Latek

Modelowanie procesów komórkowych

Białka błonowe stanowią 20-30 % ludzkiego genomu. Stanowią trudny obiekt do badań eksperymentalnych i w związku z tym jest ich znacznie mniej w Protein Data Bank niż białek globularnych. Biologia obliczeniowa stanowi uzupełnienie badań eksperymentalnych a w wielu przypadkach je zastępuje - właśnie w przypadku białek błonowych. Zajmujemy się przewidywaniem struktur białek transbłonowych metodami modelowania porównawczego i de novo, badaniem dynamiki i mechanizmów ich działania oraz projektowaniem dla nich substancji o znaczeniu farmakologicznym oraz ich optymalizacją.

Zapraszamy studentów do realizacji prac dyplomowych i doktorskich. Przykładowe tematy prac licencjackich i magisterskich: "Mechanizmy aktywacji receptora sekretynowego", "Odróżnianie agonistów od antagonistów receptorów GPCR", "Projektowanie nowych substancji czynnych modulujących działanie receptora kalcytoninowego", "Potencjały statystyczne w modelowaniu białek transbłonowych", "Badanie dynamiki kompleksu ligand-receptor na przykładzie receptora glukagonowego", "Aplikacje internetowe w modelowaniu receptorów GPCR", "Badanie mechanizmów transportu przez błonę komórkową na przykładzie rodziny transporterów nukleozydowych".

Projektowanie Leków
INPHARMA

Dynamika Molekularna
VPAC1 receptor

Modelowanie przez Homologię
GPCRM

Tworzenie Oprogramowania
Receptory GPCR

Research Topics

Modeling of cellular processes

GPCR receptors

Homology modeling of GPCR structures & drug design
Activation switches

SLC transporters

De novo structure prediction & pharmacogenomics
SLC28

Software Development

Applications for protein structure prediction & drug design
GPCRM & GUT-DOCK, CABS-NMR, INPHARMA

Protein Structure Prediction

Model building from multiple templates & sequence profiles comparison
GPCRM, GPCRDOCK 2013, De novo structure prediction, NMR-guided modeling

Molecular Dynamics

Dynamics of biological processes on a molecular level
S1P1, FPR1, class B GPCRs, VPAC1, V-ATPase

Drug Discovery

Structure-based drug design & lead optimization Glucagon receptors, VPAC1, V-ATPase, INPHARMA - NMR

Proteins in PDB
Human proteins in PDB
EM structures in PDB
Membrane proteins in PDB
Tools

Software for Computational Biology

We are not only Users but we actively contribute to scientific software. We developed two web applications for modeling of G protein-coupled receptors: GUT-DOCK & GPCRM and contributed to INPHARMA and CABS-NMR.

Our recent project is focused on: Resources for GPCR research.

GUT-DOCK

100%

GPCRM

100%

Rosetta

80%

MODELLER

80%

NAMD

80%
About us

Research Work Timeline

For publications visit: Google Scholar

Group Leader 2019-

Habilitation: "Determination of transmembrane protein structure and function considering their evolutionary diversity", Faculty of Chemistry, University of Warsaw.

SONATA - Principle Investigator 2013-2018

"Structural studies based on the low sequence similarity of G-protein coupled receptors activated by hormones and allosteric modulators.", National Science Centre in Poland, grant no DEC-2012/07/D/NZ1/04244

PhD Studies 2004-2009

PhD studies in the Laboratory of Prof. Kolinski, Faculty of Chemistry, University of Warsaw. PhD thesis title: "Protein structure determination using sparse experimental data", MNiSW grant for PhD students: „Modeling of protein structures based on fragmentary data from simple NMR experiments”.

Selected publications

GPCRs

M. Mizera, D. Latek. Ligand-receptor interactions and machine learning in GCGR and GLP-1R drug discovery. Int. J. Mol. Sci. 2021, 22(8), 4060. (IF=4.556)

I. Rodriguez-Espigares et al. GPCRmd uncovers the dynamics of the 3D-GPCRome. Nature Methods 2020, 17, 777-787. (IF=30.822)

M. Mizera, D. Latek, J. Cielecka-Piontek. Virtual Screening of C. Sativa Constituents for the Identification of Selective Ligands for Cannabinoid Receptor 2. Int. J. Mol. Sci. 2020, 21(15), 5308. (IF=4.556)

D Latek*, I Langer, KA Krzysko, L Charzewski. A Molecular Dynamics Study of Vasoactive Intestinal Peptide Receptor 1 and the Basis of Its Therapeutic Antagonism. Int. J. Mol. Sci. 2019, 20, 4348. (IF=4.556)

Latek D*, Rutkowska E, Niewieczerzal S, Cielecka-Piontek J. Drug-induced diabetes type 2: In silico study involving class B GPCRs. PLoS ONE 2019 14(1): e0208892. https://doi.org/10.1371/journal.pone.0208892 (IF=2.776)

Miszta P, Pasznik P, Jakowiecki J, Sztyler A, Latek D, Filipek S*. GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models. Nucleic Acids Res. 2018;46(W1):W387‐W395. doi:10.1093/nar/gky429 (IF=10.147)

Latek D*, Bajda M, Filipek S*. A Hybrid Approach to Structure and Function Modeling of G Protein-Coupled Receptors, J Chem Inf Model 2016, 56(4), 630-641, DOI: 10.1021/acs.jcim.5b00451 (IF=3.966)

Yuan S, Wu R, Latek D, Trzaskowski B, Filipek S*. Lipid Receptor S1P1 Activation Scheme Concluded from Microsecond All-Atom Molecular Dynamics Simulations. PLoS Comput Biol 2013, 9(10): e1003261. doi:10.1371/journal.pcbi.1003261. (IF=4.428)

Latek D*, Pasznik P, Carlomagno T & Filipek S*. Towards Improved Quality of GPCR Models by Usage of Multiple Templates and Profile-Profile Comparison. PLOS ONE 2013, 8, e56742, doi: 10.1371/journal.pone.0056742. (IF=2.776)

Yuan S, Ghoshdastider U, Trzaskowski B, Latek D, Debinski A, Pulawski W, Wu R, Gerke V & Filipek S*. The role of water in activation mechanism of human N-formyl peptide receptor 1 (FPR1) based on molecular dynamics simulations. PLOS ONE 2012, 7, e47114, doi: 10.1371/journal.pone.0047114. (IF=2.776)

Latek D, Kolinski M, Ghoshdastider U, Debinski A, Bombolewski R, Plazinska A, Jozwiak K & Filipek S*. Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic beta 2 AR. J Mol Model 2011, 17, 2353-2366, doi:10.1007/s00894-011-0986-7. (IF=1.580)

Latek D, Modzelewska A, Trzaskowski B, Palczewski K & Filipek S*. G protein-coupled receptors--recent advances. Acta Biochim Pol 2012, 59, 515-529. (IF=1.626)

Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A & Filipek S*. Action of molecular switches in GPCRs--theoretical and experimental studies. Curr Med Chem 2012, 19, 1090-1109. (IF=3.469) liczba cytowań=293

Other transmembrane proteins

Latek D. Rosetta Broker for membrane protein structure prediction: concentrative nucleoside transporter 3 and corticotropin-releasing factor receptor 1 test cases, BMC Structural Biology 2017, 17:8, DOI: 10.1186/s12900-017-0078-8. (IF=2.222)

Dreisigacker S, Latek D, Bockelmann S, Huss M, Wieczorek H, Filipek S, Gohlke H, Menche D & Carlomagno T*. Understanding the inhibitory effect of highly potent and selective archazolides binding to the vacuolar ATPase. J Chem Inf Model 2012, 52, 2265-2272, doi: 10.1021/ci300242d. (IF=3.966)

NMR

Latek D* & Kolinski A. CABS-NMR--De novo tool for rapid global fold determination from chemical shifts, residual dipolar couplings and sparse methyl-methyl NOEs. J Comput Chem 2011, 32, 536-544, doi: 10.1002/jcc.21640. (IF=3.194)

Latek D*, Ekonomiuk D & Kolinski A. Protein structure prediction: combining de novo modeling with sparse experimental data. J Comput Chem 2007, 28, 1668-1676, doi: 10.1002/jcc.20657. (IF=3.194)

Codutti L, Skjaerven L, Angelini A, Grimaldi M, Latek D, Monecke P, Dreyer M & Carlomagno T*. Accounting for conformational variability in protein-ligand docking with NMR-guided rescoring. J Am Chem Soc 2013, 135(15), 5819-27. (IF=14.695)

For Students

Materiały do zajęć

Ćwiczenia rachunkowe z chemi analitycznej

Zadania powtórzeniowe

Monographs and others

D Latek, B Trzaskowski, S Niewieczerzał, P Miszta, K Młynarczyk, A Dębiński, W Puławski, S Yuan, A Sztyler, U Orzeł, J Jakowiecki, S Filipek*. Modeling of Membrane Proteins. In: Liwo A. (eds) Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes. Springer Series on Bio- and Neurosystems, 2019, vol 8. Springer, Cham

Gront D, Latek D, Kurcinski M & Kolinski A*. (2008) Template-Free Predictions of Three-Dimensional Protein Structures: From First Principles to Knowledge-Based Potentials. In Prediction of Protein Structures, Functions, and Interactions, pp. 117-141. John Wiley & Sons, Ltd.

Kufareva I, Katritch V, Participants of GPCR Dock 2013, Stevens RCS, Abagyan R. (2014) Advances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment: Meeting New Challenges. Structure , 22(8) , 1120 – 1139

Read

Recent Blog

HTML5 Bootstrap Template by colorlib.com
October 24, 2019 | Drug Discovery

Toward G protein-coupled receptor structure-based drug design using X-ray lasers

'Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process.[...] Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein.'

HTML5 Bootstrap Template by colorlib.com
November 18, 2019 | GPCR receptors

Structure of an endosomal signaling GPCR-G protein-Beta-arrestin megacomplex

'Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by Beta-arrestin (Beta-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR–G protein–Beta-arr ‘megaplex’. [...] Here, we present its cryo-electron microscopy structure'

HTML5 Bootstrap Template by colorlib.com
November 4, 2019 | Protein Structure

Membrane protein megahertz crystallography at the European XFEL

'The world’s first superconducting megahertz repetition rate hard X-ray free-electron laser (XFEL), the European XFEL, began operation in 2017, featuring a unique pulse train structure with 886 ns between pulses. [...] Here, we report the first membrane protein megahertz SFX experiment, where we determined a 2.9 Å-resolution SFX structure of the large membrane protein complex, Photosystem I, a > 1 MDa complex containing 36 protein subunits and 381 cofactors.'

Contact

Modeling of
cellular processes
research group

dlatek at chem.uw.edu.pl

Faculty of Chemistry UW
1 Pasteur St., 02-093 Warsaw

+48-22-55-26-236