Protonation patterns in reduced and oxidized form of electron transfer proteins

Dobrev, Plamen

dc.contributor.advisor	Grubmüller, Helmut Prof. Dr.	de
dc.contributor.author	Dobrev, Plamen	de
dc.date.accessioned	2012-10-23T18:36:31Z	de
dc.date.accessioned	2013-01-18T14:27:48Z	de
dc.date.available	2013-01-30T23:50:19Z	de
dc.date.issued	2012-10-23	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-000D-F0C2-8	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3280
dc.description.abstract	Die 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 konformativen	de
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	de
dc.title	Protonation patterns in reduced and oxidized form of electron transfer proteins	de
dc.type	doctoralThesis	de
dc.title.translated	Protonierungsmuster von Elektron-Transfer-Proteinen in reduzierter und oxidierter Form	de
dc.contributor.referee	Grubmüller, Helmut Prof. Dr.	de
dc.date.examination	2012-05-08	de
dc.subject.dnb	500 Naturwissenschaften	de
dc.subject.gok	WC 000	de
dc.description.abstracteng	The 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.coReferee	Müller, Marcus Prof. Dr.	de
dc.contributor.thirdReferee	Steinem, Claudia Prof. Dr.	de
dc.subject.topic	Göttingen Graduate School for Neurosciences and Molecular Biosciences (GGNB)	de
dc.subject.ger	pKa-Werte	de
dc.subject.ger	Molekulardynamik	de
dc.subject.ger	Molekulardynamik Simulationen mit explizitem Lösemittel und kontantem pH-Wert	de
dc.subject.ger	Cytochrom C aus Rhodopseudomonas viridis	de
dc.subject.ger	epidermaler Wachstumsfaktor	de
dc.subject.ger	Cardiotoxin	de
dc.subject.ger	Titratio	de
dc.subject.eng	pKa	de
dc.subject.eng	Molecular Dynamics	de
dc.subject.eng	explicit silvent constant pH MD	de
dc.subject.eng	Cytochrome C from Rhodopseudomonas viridis	de
dc.subject.eng	Epidermal Growth Factor	de
dc.subject.eng	Cardiotoxin	de
dc.subject.eng	titration	de
dc.subject.bk	30	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-3747-9	de
dc.identifier.purl	webdoc-3747	de
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften und Molekulare Biowissenschaften (GGNB)	de
dc.identifier.ppn	731468341	de

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GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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