TY - THES AU - Farkas, Bianka Vivien TI - A CFTR kloridcsatorna vizsgálata molekula dinamika szimulációk segítségével PB - Pázmány Péter Katolikus Egyetem (PPKE) PY - 2023 SP - 107 DO - 10.15774/PPKE.ITK.2023.006 UR - https://m2.mtmt.hu/api/publication/34206953 ID - 34206953 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Padányi, Rita AU - Farkas, Bianka Vivien AU - Tordai, Hedvig AU - Kiss, Bálint AU - Grubmüller, Helmut AU - Soya, Naoto AU - Lukács, Gergely L. AU - Kellermayer, Miklós AU - Hegedűs, Tamás TI - Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1 JF - COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL J2 - CSBJ VL - 20 PY - 2022 SP - 2587 EP - 2599 PG - 13 SN - 2001-0370 DO - 10.1016/j.csbj.2022.05.036 UR - https://m2.mtmt.hu/api/publication/32853643 ID - 32853643 AB - Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (DF508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The DF508 compromises the folding energetics of the NBD1, as well as the folding of three other CFTR domains. Combination of FDA approved corrector molecules can efficiently but incompletely rescue the DF508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wildtype-like conformational stability of the DF508-NBD1 would be highly beneficial. The most prominent molecule, 5-bromoindole-3-acetic acid (BIA) that can thermally stabilize the NBD1 has low potency and efficacy. To gain insights into the NBD1 (un)folding dynamics and BIA binding site localization, we combined molecular dynamics (MD) simulations, atomic force spectroscopy (AFM) and hydrogendeuterium exchange (HDX) experiments. We found that the NBD1 a-subdomain with three adjacent strands from the b-subdomain plays an important role in early folding steps, when crucial non-native interactions are formed via residue F508. Our AFM and HDX experiments showed that BIA associates with this a-core region and increases the resistance of the DF508-NBD1 against mechanical unfolding, a phenomenon that could be exploited in future developments of folding correctors. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Tamás AU - Geisler, Markus AU - Lukács, Gergely László AU - Farkas, Bianka Vivien TI - Ins and outs of AlphaFold2 transmembrane protein structure predictions JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 79 PY - 2022 IS - 1 PG - 12 SN - 1420-682X DO - 10.1007/s00018-021-04112-1 UR - https://m2.mtmt.hu/api/publication/32612583 ID - 32612583 LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien TI - Effect of F508 deletion on the CFTR NBD1 nanomechanics JF - PHD PROCEEDINGS ANNUAL ISSUES OF THE DOCTORAL SCHOOL FACULTY OF INFORMATION TECHNOLOGY AND BIONICS J2 - PHD PROC PPKE IT VL - 16 PY - 2021 SP - 33 SN - 2064-7271 UR - https://m2.mtmt.hu/api/publication/32499276 ID - 32499276 LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien TI - Mechanical unfolding of the CFTR chloride channel NBD1 domain using force probe simulations JF - PHD PROCEEDINGS ANNUAL ISSUES OF THE DOCTORAL SCHOOL FACULTY OF INFORMATION TECHNOLOGY AND BIONICS J2 - PHD PROC PPKE IT VL - 15 PY - 2020 SP - 33 SN - 2064-7271 UR - https://m2.mtmt.hu/api/publication/32499230 ID - 32499230 LA - English DB - MTMT ER - TY - CONF AU - Farkas, Bianka Vivien AU - R., Padányi AU - Tordai, Hedvig AU - B., Kiss AU - M., Kellermayer AU - T., Hegedűs TI - Nanomechanics of the CFTR NBD1 T2 - ABC2020 - 8th FEBS Special Meeting PY - 2020 SP - 77 UR - https://m2.mtmt.hu/api/publication/31363671 ID - 31363671 LA - English DB - MTMT ER - TY - JOUR AU - Gáspárné Csizmadia, Georgina AU - Farkas, Bianka Vivien AU - Katona, E. AU - Tusnády, Gábor AU - Hegedűs, Tamás TI - Using MemBlob to Analyze Transmembrane Regions Based on Cryo-EM Maps JF - METHODS IN MOLECULAR BIOLOGY J2 - METHODS MOL BIOL VL - 2112 PY - 2020 SP - 123 EP - 130 PG - 8 SN - 1064-3745 DO - 10.1007/978-1-0716-0270-6_9 UR - https://m2.mtmt.hu/api/publication/31177534 ID - 31177534 AB - Transmembrane proteins include membrane channels, pores, and receptors and, as such, comprise an important part of the proteome, yet our knowledge about them is much less complete than about soluble, globular proteins. An important aspect of transmembrane protein structure is their exact position within the lipid bilayer, a feature hard to investigate experimentally at the atomic level. Here we describe MemBlob, a novel approach utilizing difference electron density maps obtained by cryo-EM studies of transmembrane proteins. The idea behind is that the nonprotein part of such maps carries information on the exact localization of the membrane mimetics used in the experiment and can be used to extract the positional information of the protein within the membrane. MemBlob uses a structural model of the protein and an experimental electron density map to provide an estimation of the surface residues interacting with the membrane. LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien AU - Gáspárné Csizmadia, Georgina AU - Katona, Eszter AU - Tusnády, Gábor AU - Hegedűs, Tamás TI - MemBlob database and server for identifying transmembrane regions using cryo-EM maps JF - BIOINFORMATICS J2 - BIOINFORMATICS VL - 36 PY - 2020 IS - 8 SP - 2595 EP - 2598 PG - 4 SN - 1367-4803 DO - 10.1093/bioinformatics/btz539 UR - https://m2.mtmt.hu/api/publication/30745372 ID - 30745372 N1 - Cited By :2 Export Date: 15 May 2020 Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, 1094, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, 1083, Hungary Faculty of Brain Sciences, University College London, London, W1T 7NF, United Kingdom 'Momentum' Membrane Protein Bioinformatics Research Group, Institute of Enzymology, RCNS, Hungarian Academy of Sciences, Budapest, 1117, Hungary Cited By :2 Export Date: 24 July 2020 CODEN: BOINF Correspondence Address: Hegedus, T.; Department of Biophysics and Radiation Biology, Semmelweis UniversityHungary; email: tamas.hegedus@hegelab.org Funding details: HEGEDU18I0 Funding details: K127961, K125607, K119287, K111678 Funding details: Cystic Fibrosis Foundation Funding text 1: This work was supported by the National Research, Development and Innovation Office [K111678, K119287, K125607, K127961], the Cystic Fibrosis Foundation [CFF HEGEDU18I0] and the Semmelweis Science and Innovation Fund. AB - The identification of transmembrane helices in transmembrane proteins is crucial, not only to understand their mechanism of action, but also to develop new therapies. While experimental data on the boundaries of membrane-embedded regions is sparse, this information is present in cryo-electron microscopy (cryo-EM) density maps and it has not been utilized yet for determining membrane regions. We developed a computational pipeline, where the inputs of a cryo-EM map, the corresponding atomistic structure, and the potential bilayer orientation determined by TMDET algorithm of a given protein result in an output defining the residues assigned to the bulk water phase, lipid interface, and the lipid hydrophobic core. Based on this method, we built a database involving published cryo-EM protein structures and a server to be able to compute this data for newly obtained structures.http://memblob.hegelab.org.Supplementary data are available at Bioinformatics online. LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien AU - Tordai, Hedvig AU - Padányi, Rita AU - Tordai, Attila AU - Gera, János AU - Paragi, Gábor AU - Hegedűs, Tamás TI - Discovering the chloride pathway in the CFTR channel JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 77 PY - 2020 IS - 4 SP - 765 EP - 778 PG - 12 SN - 1420-682X DO - 10.1007/s00018-019-03211-4 UR - https://m2.mtmt.hu/api/publication/30745347 ID - 30745347 N1 - Funding Agency and Grant Number: Semmelweis Egyetem [Sci_Innov18] Funding Source: Medline; Cystic Fibrosis Foundation (US) [HEGEDU18I0] Funding Source: Medline; Nemzeti Kutatasi, Fejlesztesi es Innovacios Hivatal (HU) [K127961, K111678] Funding Source: Medline Cited By :2 Export Date: 31 August 2021 CODEN: CMLSF Correspondence Address: Hegedűs, T.; Department of Biophysics and Radiation Biology, Hungary; email: hegedus@hegelab.org LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien TI - Describing the ion passage through the CFTR ion channel JF - PHD PROCEEDINGS ANNUAL ISSUES OF THE DOCTORAL SCHOOL FACULTY OF INFORMATION TECHNOLOGY AND BIONICS J2 - PHD PROC PPKE IT VL - 14 PY - 2019 IS - 2019 SP - 31 SN - 2064-7271 UR - https://m2.mtmt.hu/api/publication/32499209 ID - 32499209 LA - English DB - MTMT ER -