LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Erweiterte Suche

Suchergebnis

Treffer 1 - 4 von insgesamt 4

Suchoptionen

  1. Artikel ; Online: Correction to Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex.

    Zhang, Ivy / Rufa, Dominic A / Pulido, Iván / Henry, Michael M / Rosen, Laura E / Hauser, Kevin / Singh, Sukrit / Chodera, John D

    Journal of chemical theory and computation

    2024  Band 20, Heft 2, Seite(n) 990–991

    Sprache Englisch
    Erscheinungsdatum 2024-01-02
    Erscheinungsland United States
    Dokumenttyp Published Erratum
    ISSN 1549-9626
    ISSN (online) 1549-9626
    DOI 10.1021/acs.jctc.3c01298
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  2. Artikel ; Online: Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex.

    Zhang, Ivy / Rufa, Dominic A / Pulido, Iván / Henry, Michael M / Rosen, Laura E / Hauser, Kevin / Singh, Sukrit / Chodera, John D

    Journal of chemical theory and computation

    2023  Band 19, Heft 15, Seite(n) 4863–4882

    Abstract: Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on ... ...

    Abstract Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on protein:protein binding affinities, but these calculations can involve sampling challenges due to the complex networks of protein and water interactions frequently present in protein:protein interfaces. We investigate these challenges by extending a graphics processing unit (GPU)-accelerated open-source relative free energy calculation package (Perses) to predict the impact of amino acid mutations on protein:protein binding. Using the well-characterized model system barnase:barstar, we describe analyses for identifying and characterizing sampling problems in protein:protein relative free energy calculations. We find that mutations with sampling problems often involve charge-changes, and inadequate sampling can be attributed to slow degrees of freedom that are mutation-specific. We also explore the accuracy and efficiency of current state-of-the-art approaches─alchemical replica exchange and alchemical replica exchange with solute tempering─for overcoming relevant sampling problems. By employing sufficiently long simulations, we achieve accurate predictions (RMSE 1.61, 95% CI: [1.12, 2.11] kcal/mol), with 86% of estimates within 1 kcal/mol of the experimentally determined relative binding free energies and 100% of predictions correctly classifying the sign of the changes in binding free energies. Ultimately, we provide a model workflow for applying protein mutation free energy calculations to protein:protein complexes, and importantly, catalog the sampling challenges associated with these types of alchemical transformations. Our free open-source package (Perses) is based on OpenMM and is available at https://github.com/choderalab/perses.
    Mesh-Begriff(e) Thermodynamics ; Molecular Dynamics Simulation ; Entropy ; Protein Binding ; Amino Acids
    Chemische Substanzen Amino Acids
    Sprache Englisch
    Erscheinungsdatum 2023-07-14
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 1549-9626
    ISSN (online) 1549-9626
    DOI 10.1021/acs.jctc.3c00333
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  3. Artikel: Identifying and overcoming the sampling challenges in relative binding free energy calculations of a model protein:protein complex.

    Zhang, Ivy / Rufa, Dominic A / Pulido, Iván / Henry, Michael M / Rosen, Laura E / Hauser, Kevin / Singh, Sukrit / Chodera, John D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on ... ...

    Abstract Relative alchemical binding free energy calculations are routinely used in drug discovery projects to optimize the affinity of small molecules for their drug targets. Alchemical methods can also be used to estimate the impact of amino acid mutations on protein:protein binding affinities, but these calculations can involve sampling challenges due to the complex networks of protein and water interactions frequently present in protein:protein interfaces. We investigate these challenges by extending a GPU-accelerated open-source relative free energy calculation package (Perses) to predict the impact of amino acid mutations on protein:protein binding. Using the well-characterized model system barnase:barstar, we describe analyses for identifying and characterizing sampling problems in protein:protein relative free energy calculations. We find that mutations with sampling problems often involve charge-changes, and inadequate sampling can be attributed to slow degrees of freedom that are mutation-specific. We also explore the accuracy and efficiency of current state-of-the-art approaches-alchemical replica exchange and alchemical replica exchange with solute tempering-for overcoming relevant sampling problems. By employing sufficiently long simulations, we achieve accurate predictions (RMSE 1.61, 95% CI: [1.12, 2.11] kcal/mol), with 86% of estimates within 1 kcal/mol of the experimentally-determined relative binding free energies and 100% of predictions correctly classifying the sign of the changes in binding free energies. Ultimately, we provide a model workflow for applying protein mutation free energy calculations to protein:protein complexes, and importantly, catalog the sampling challenges associated with these types of alchemical transformations. Our free open-source package (Perses) is based on OpenMM and available at https://github.com/choderalab/perses .
    Sprache Englisch
    Erscheinungsdatum 2023-06-21
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.03.07.530278
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  4. Artikel ; Online: Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.

    Boby, Melissa L / Fearon, Daren / Ferla, Matteo / Filep, Mihajlo / Koekemoer, Lizbé / Robinson, Matthew C / Chodera, John D / Lee, Alpha A / London, Nir / von Delft, Annette / von Delft, Frank / Achdout, Hagit / Aimon, Anthony / Alonzi, Dominic S / Arbon, Robert / Aschenbrenner, Jasmin C / Balcomb, Blake H / Bar-David, Elad / Barr, Haim /
    Ben-Shmuel, Amir / Bennett, James / Bilenko, Vitaliy A / Borden, Bruce / Boulet, Pascale / Bowman, Gregory R / Brewitz, Lennart / Brun, Juliane / Bvnbs, Sarma / Calmiano, Mark / Carbery, Anna / Carney, Daniel W / Cattermole, Emma / Chang, Edcon / Chernyshenko, Eugene / Clyde, Austin / Coffland, Joseph E / Cohen, Galit / Cole, Jason C / Contini, Alessandro / Cox, Lisa / Croll, Tristan Ian / Cvitkovic, Milan / De Jonghe, Steven / Dias, Alex / Donckers, Kim / Dotson, David L / Douangamath, Alice / Duberstein, Shirly / Dudgeon, Tim / Dunnett, Louise E / Eastman, Peter / Erez, Noam / Eyermann, Charles J / Fairhead, Michael / Fate, Gwen / Fedorov, Oleg / Fernandes, Rafaela S / Ferrins, Lori / Foster, Richard / Foster, Holly / Fraisse, Laurent / Gabizon, Ronen / García-Sastre, Adolfo / Gawriljuk, Victor O / Gehrtz, Paul / Gileadi, Carina / Giroud, Charline / Glass, William G / Glen, Robert C / Glinert, Itai / Godoy, Andre S / Gorichko, Marian / Gorrie-Stone, Tyler / Griffen, Ed J / Haneef, Amna / Hassell Hart, Storm / Heer, Jag / Henry, Michael / Hill, Michelle / Horrell, Sam / Huang, Qiu Yu Judy / Huliak, Victor D / Hurley, Matthew F D / Israely, Tomer / Jajack, Andrew / Jansen, Jitske / Jnoff, Eric / Jochmans, Dirk / John, Tobias / Kaminow, Benjamin / Kang, Lulu / Kantsadi, Anastassia L / Kenny, Peter W / Kiappes, J L / Kinakh, Serhii O / Kovar, Boris / Krojer, Tobias / La, Van Ngoc Thuy / Laghnimi-Hahn, Sophie / Lefker, Bruce A / Levy, Haim / Lithgo, Ryan M / Logvinenko, Ivan G / Lukacik, Petra / Macdonald, Hannah Bruce / MacLean, Elizabeth M / Makower, Laetitia L / Malla, Tika R / Marples, Peter G / Matviiuk, Tatiana / McCorkindale, Willam / McGovern, Briana L / Melamed, Sharon / Melnykov, Kostiantyn P / Michurin, Oleg / Miesen, Pascal / Mikolajek, Halina / Milne, Bruce F / Minh, David / Morris, Aaron / Morris, Garrett M / Morwitzer, Melody Jane / Moustakas, Demetri / Mowbray, Charles E / Nakamura, Aline M / Neto, Jose Brandao / Neyts, Johan / Nguyen, Luong / Noske, Gabriela D / Oleinikovas, Vladas / Oliva, Glaucius / Overheul, Gijs J / Owen, C David / Pai, Ruby / Pan, Jin / Paran, Nir / Payne, Alexander Matthew / Perry, Benjamin / Pingle, Maneesh / Pinjari, Jakir / Politi, Boaz / Powell, Ailsa / Pšenák, Vladimír / Pulido, Iván / Puni, Reut / Rangel, Victor L / Reddi, Rambabu N / Rees, Paul / Reid, St Patrick / Reid, Lauren / Resnick, Efrat / Ripka, Emily Grace / Robinson, Ralph P / Rodriguez-Guerra, Jaime / Rosales, Romel / Rufa, Dominic A / Saar, Kadi / Saikatendu, Kumar Singh / Salah, Eidarus / Schaller, David / Scheen, Jenke / Schiffer, Celia A / Schofield, Christopher J / Shafeev, Mikhail / Shaikh, Aarif / Shaqra, Ala M / Shi, Jiye / Shurrush, Khriesto / Singh, Sukrit / Sittner, Assa / Sjö, Peter / Skyner, Rachael / Smalley, Adam / Smeets, Bart / Smilova, Mihaela D / Solmesky, Leonardo J / Spencer, John / Strain-Damerell, Claire / Swamy, Vishwanath / Tamir, Hadas / Taylor, Jenny C / Tennant, Rachael E / Thompson, Warren / Thompson, Andrew / Tomásio, Susana / Tomlinson, Charles W E / Tsurupa, Igor S / Tumber, Anthony / Vakonakis, Ioannis / van Rij, Ronald P / Vangeel, Laura / Varghese, Finny S / Vaschetto, Mariana / Vitner, Einat B / Voelz, Vincent / Volkamer, Andrea / Walsh, Martin A / Ward, Walter / Weatherall, Charlie / Weiss, Shay / White, Kris M / Wild, Conor Francis / Witt, Karolina D / Wittmann, Matthew / Wright, Nathan / Yahalom-Ronen, Yfat / Yilmaz, Nese Kurt / Zaidmann, Daniel / Zhang, Ivy / Zidane, Hadeer / Zitzmann, Nicole / Zvornicanin, Sarah N

    Science (New York, N.Y.)

    2023  Band 382, Heft 6671, Seite(n) eabo7201

    Abstract: We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, ... ...

    Abstract We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.
    Mesh-Begriff(e) Humans ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Molecular Docking Simulation ; SARS-CoV-2 ; Drug Discovery ; Coronavirus Protease Inhibitors/chemical synthesis ; Coronavirus Protease Inhibitors/chemistry ; Coronavirus Protease Inhibitors/pharmacology ; Structure-Activity Relationship ; COVID-19 Drug Treatment ; Crystallography, X-Ray
    Chemische Substanzen 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; Coronavirus Protease Inhibitors
    Sprache Englisch
    Erscheinungsdatum 2023-11-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abo7201
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 27: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 77: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

Zum Seitenanfang