Gapsys, Vytautas

[["dc.bibliographiccitation.firstpage","299"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Biomolecular NMR"],["dc.bibliographiccitation.lastpage","307"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Narayanan, Raghavendran L."],["dc.contributor.author","Xiang, ShengQi"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:49:30Z"],["dc.date.available","2018-11-07T09:49:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Intrinsically disordered proteins (IDPs) are best described by ensembles of conformations and a variety of approaches have been developed to determine IDP ensembles. Because of the large number of conformations, however, cross-validation of the determined ensembles by independent experimental data is crucial. The (1)J(C alpha H alpha) coupling constant is particularly suited for cross-validation, because it has a large magnitude and mostly depends on the often less accessible dihedral angle psi. Here, we reinvestigated the connection between (1)J(C alpha H alpha) values and protein backbone dihedral angles. We show that accurate amino-acid specific random coil values of the (1)J(C alpha H alpha) coupling constant, in combination with a reparameterized empirical Karplus-type equation, allow for reliable cross-validation of molecular ensembles of IDPs."],["dc.description.sponsorship","DFG [ZW71/8-1]"],["dc.identifier.doi","10.1007/s10858-015-9990-z"],["dc.identifier.isi","000365088800008"],["dc.identifier.pmid","26433382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35521"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-5001"],["dc.relation.issn","0925-2738"],["dc.title","Improved validation of IDP ensembles by one-bond C alpha-H alpha scalar couplings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","acs.jcim.2c00044"],["dc.bibliographiccitation.journal","Journal of Chemical Information and Modeling"],["dc.contributor.author","Kutzner, Carsten"],["dc.contributor.author","Kniep, Christian"],["dc.contributor.author","Cherian, Austin"],["dc.contributor.author","Nordstrom, Ludvig"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Gapsys, Vytautas"],["dc.date.accessioned","2022-04-01T10:01:40Z"],["dc.date.available","2022-04-01T10:01:40Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1021/acs.jcim.2c00044"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105722"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1549-960X"],["dc.relation.issn","1549-9596"],["dc.title","GROMACS in the Cloud: A Global Supercomputer to Speed Up Alchemical Drug Design"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:59:19Z"],["dc.date.available","2021-03-05T08:59:19Z"],["dc.date.issued","2019"],["dc.description.abstract","A recent molecular dynamics investigation into the stability of hemoglobin concluded that the unliganded protein is only stable in the T state when a solvent box is used in the simulations that is ten times larger than what is usually employed (El Hage et al., 2018). Here, we express three main concerns about that study. In addition, we find that with an order of magnitude more statistics, the reported box size dependence is not reproducible. Overall, no significant effects on the kinetics or thermodynamics of conformational transitions were observed."],["dc.identifier.doi","10.7554/eLife.44718"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80424"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.eissn","2050-084X"],["dc.title","Comment on 'Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size'"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4241"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","The Journal of Physical Chemistry B"],["dc.bibliographiccitation.lastpage","4261"],["dc.bibliographiccitation.volume","125"],["dc.contributor.author","Baumann, Hannah M."],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Mobley, David L."],["dc.date.accessioned","2022-03-01T11:45:40Z"],["dc.date.available","2022-03-01T11:45:40Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1021/acs.jpcb.0c10263"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103409"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1520-5207"],["dc.relation.issn","1520-6106"],["dc.title","Challenges Encountered Applying Equilibrium and Nonequilibrium Binding Free Energy Calculations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","61"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Communications Chemistry"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Yildirim, Ahmet"],["dc.contributor.author","Aldeghi, Matteo"],["dc.contributor.author","Khalak, Yuriy"],["dc.contributor.author","van der Spoel, David"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2022-03-01T11:46:05Z"],["dc.date.available","2022-03-01T11:46:05Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The accurate calculation of the binding free energy for arbitrary ligand–protein pairs is a considerable challenge in computer-aided drug discovery. Recently, it has been demonstrated that current state-of-the-art molecular dynamics (MD) based methods are capable of making highly accurate predictions. Conventional MD-based approaches rely on the first principles of statistical mechanics and assume equilibrium sampling of the phase space. In the current work we demonstrate that accurate absolute binding free energies (ABFE) can also be obtained via theoretically rigorous non-equilibrium approaches. Our investigation of ligands binding to bromodomains and T4 lysozyme reveals that both equilibrium and non-equilibrium approaches converge to the same results. The non-equilibrium approach achieves the same level of accuracy and convergence as an equilibrium free energy perturbation (FEP) method enhanced by Hamiltonian replica exchange. We also compare uni- and bi-directional non-equilibrium approaches and demonstrate that considering the work distributions from both forward and reverse directions provides substantial accuracy gains. In summary, non-equilibrium ABFE calculations are shown to yield reliable and well-converged estimates of protein–ligand binding affinity."],["dc.description.abstract","Abstract The accurate calculation of the binding free energy for arbitrary ligand–protein pairs is a considerable challenge in computer-aided drug discovery. Recently, it has been demonstrated that current state-of-the-art molecular dynamics (MD) based methods are capable of making highly accurate predictions. Conventional MD-based approaches rely on the first principles of statistical mechanics and assume equilibrium sampling of the phase space. In the current work we demonstrate that accurate absolute binding free energies (ABFE) can also be obtained via theoretically rigorous non-equilibrium approaches. Our investigation of ligands binding to bromodomains and T4 lysozyme reveals that both equilibrium and non-equilibrium approaches converge to the same results. The non-equilibrium approach achieves the same level of accuracy and convergence as an equilibrium free energy perturbation (FEP) method enhanced by Hamiltonian replica exchange. We also compare uni- and bi-directional non-equilibrium approaches and demonstrate that considering the work distributions from both forward and reverse directions provides substantial accuracy gains. In summary, non-equilibrium ABFE calculations are shown to yield reliable and well-converged estimates of protein–ligand binding affinity."],["dc.identifier.doi","10.1038/s42004-021-00498-y"],["dc.identifier.pii","498"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103552"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2399-3669"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Accurate absolute free energies for ligand–protein binding based on non-equilibrium approaches"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","49"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Computer-Aided Molecular Design"],["dc.bibliographiccitation.lastpage","61"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Khalak, Yuriy"],["dc.contributor.author","Tresadern, Gary"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Gapsys, Vytautas"],["dc.date.accessioned","2021-03-05T09:05:21Z"],["dc.date.available","2021-03-05T09:05:21Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s10822-020-00359-1"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80449"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.eissn","1573-4951"],["dc.relation.issn","0920-654X"],["dc.title","Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2162"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","2174"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Xiang, Shengqi"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Kim, Hai-Young"],["dc.contributor.author","Bessonov, Sergey"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Moehlmann, Sina"],["dc.contributor.author","Klaukien, Volker"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Groot, Bert L. de"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:46:59Z"],["dc.date.available","2017-09-07T11:46:59Z"],["dc.date.issued","2013"],["dc.description.abstract","Serine/arginine-rich (SR) proteins are important players in RNA metabolism and are extensively phosphorylated at serine residues in RS repeats. Here, we show that phosphorylation switches the RS domain of the serine/arginine-rich splicing factor 1 from a fully disordered state to a partially rigidified arch-like structure. Nuclear magnetic resonance spectroscopy in combination with molecular dynamics simulations revealed that the conformational switch is restricted to RS repeats, critically depends on the phosphate charge state and strongly decreases the conformational entropy of RS domains. The dynamic switch also occurs in the 100 kDa SR-related protein hPrp28, for which phosphorylation at the RS repeat is required for spliceosome assembly. Thus, a phosphorylation-induced dynamic switch is common to the class of serine/arginine-rich proteins and provides a molecular basis for the functional redundancy of serine/arginine-rich proteins and the profound influence of RS domain phosphorylation on protein-protein and protein-RNA interactions."],["dc.identifier.doi","10.1016/j.str.2013.09.014"],["dc.identifier.gro","3142236"],["dc.identifier.isi","000328914900010"],["dc.identifier.pmid","24183573"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6043"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1878-4186"],["dc.relation.issn","0969-2126"],["dc.title","Phosphorylation Drives a Dynamic Switch in Serine/Arginine-Rich Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Brennecke, Julian T."],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:58:33Z"],["dc.date.available","2021-03-05T08:58:33Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1038/srep33156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80179"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.eissn","2045-2322"],["dc.title","An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","196"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","207"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:57:54Z"],["dc.date.available","2021-03-05T08:57:54Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.bpj.2012.11.003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79923"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0006-3495"],["dc.title","Optimal Superpositioning of Flexible Molecule Ensembles"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","674a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:58:02Z"],["dc.date.available","2021-03-05T08:58:02Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.bpj.2017.11.3634"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79980"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0006-3495"],["dc.title","A Unified Framework for Alchemical Mutations in Proteins, DNA and Ligands"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]