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Protonation patterns in reduced and oxidized form of electron transfer proteins

dc.contributor.advisorGrubmüller, Helmut Prof.
dc.contributor.authorDobrev, Plamende
dc.description.abstractDie pKa-Werte ionisierbarer Aminosäuren sind essentiell für die Funktion vieler Proteine. Sie sind die Schlüsselfaktoren, welche die elektrostatischen Potentiale und ihre dreidimensionale Verteilung bestimmen, welche wiederum die enzymatische Katalyse beeinflussen und optimieren. Ferner können pKa-Werte und Protonierungszustand bei konformativende
dc.titleProtonation patterns in reduced and oxidized form of electron transfer proteinsde
dc.title.translatedProtonierungsmuster von Elektron-Transfer-Proteinen in reduzierter und oxidierter Formde
dc.contributor.refereeGrubmüller, Helmut Prof.
dc.subject.dnb500 Naturwissenschaftende
dc.subject.gokWC 000de
dc.description.abstractengThe pKa's of the ionizable amino acids are crucial for the function of many proteins as they are key factors that determine their electrostatic potential and its spatial distribution, often controlling and optimizing enzymatic catalysis. Further, during conformational motions pKa's and protonation states particularly of histidines may change. In established force field simulation, however, this effect is typically not included, and protonation states must therefore be either guessed or derived from experiment. There have been a number of approaches to include protonation effects within simulations in the past, mainly based on continuum electrostatics or implicit solvent molecular dynamics [1--3]. However, the continuum electrostatics method lack the effect of the hydrogen bonding and the entropy effects due to the dynamics of the protein and the solvent whereas the implicit solvent MD although capturing the dynamics, again misses the hydrogen bonding and entropy contribution that comes from the solvent. In this work we used the implementation and application of a dynamic protonation atomistic simulation method with explicit solvent, fast and at relatively low computational cost [4]. This approach also allows for explicit solvent constant pH MD simulations, previously developed also in our group [4], and thus is used here to calculate the pKa's of the ionzable groups in proteins. In order to validate our method, we selected a number of prototypic proteins and calculated titration curves and pKa values from constant pH simulations at a range of different pH values and compared our results with the experimental data. In the next step, we applied our model to protein that can undergo reduction and oxidation and compare the behavior of the protonatable groups in their both states. This approach will help us better understand the complicated events during electron transfer in atomistic details. 1. Lee, M. S., Salsbury, F. R., Jr., and Brooks, C. L., III (2004), Proteins 56, 738-752. 2. Khandogin J, Brooks CL 3rd., Biophys J. 2005 Jul;89(1):141-57. Epub 2005 Apr 29. 3. Mongan, J.; Case, D. A.; McCammon, J. A. J., Comput. Chem. 2004, 25, 2038–2048 4. Donnini S, Tegeler F, Groenhof G, Grubmüller H., J. Chem Theory and Comp 7: 1962- 1978 (2011)de
dc.contributor.coRefereeMüller, Marcus Prof.
dc.contributor.thirdRefereeSteinem, Claudia Prof.
dc.subject.topicGöttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB)de
dc.subject.gerMolekulardynamik Simulationen mit explizitem Lösemittel und kontantem pH-Wertde
dc.subject.gerCytochrom C aus Rhodopseudomonas viridisde
dc.subject.gerepidermaler Wachstumsfaktorde
dc.subject.engMolecular Dynamicsde
dc.subject.engexplicit silvent constant pH MDde
dc.subject.engCytochrome C from Rhodopseudomonas viridisde
dc.subject.engEpidermal Growth Factorde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften und Molekulare Biowissenschaften (GGNB)de

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