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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Molecular Modeling of Single and Multiple Beta-Sheets ofAmyloid Beta Protein 25 – 35Vita Duka 1,2 , Isabella Bestel 3 , Cezary Czaplewski 4 , Adam Liwo 4 , andInta Liepina 21 Faculty of Physics and Mathematics, University of Latvia, Zellu iela 8, Riga LV1002,Latvia, 2 Latvian Institute of Organic Synthesis, Aizkraukles str. 21, Riga LV1006, Latvia,3 Victor Segalen University of Bordeaux II, 146 rue Leo-Saignat, 33076, Bordeaux cedex,France, 4 Department of Chemistry, and University of Gdansk, ul. Sobieskiego 18, 80-952,Gdansk, PolandIntroductionAmyloidosis is misfolding and self-assembled aggregation of soluble proteins in insolublefibrils which replace the functional cells or block connections between the cells. Themechanism of amyloid formation is still unclear [1]. Amyloid beta protein 1-42 isresponsible for formation of human amyloidosis leading to Alzheimer disease [2].The present work studied the formation of amyloid -structure of the amyloid betaprotein fragment 25-35 (Abeta 25-35):Gly25-Ser26-Asn27-Lys28-Gly29-Ala30-Ile31-Ile32-Gly33-Leu34-Met35A flat, paralel single six-stranded beta-sheet (6Abeta 25-35) and ten-stranded betasheet(10Abeta 25-35) of Abeta 25-35 were constructed using a single strand of Abeta25-35 peptide. Both systems, 6Abeta 25-35 and 10Abeta 25-35, were surrounded bychlorine counterions to neutralize the system, and by a 5 Å layer of explicit watermolecules and subjected to molecular dynamics (MD) simulations in a periodic box usingAmber 9.0, f99 force field and isothermal-isobaric ensemble, NTP protocol (constanttemperature, pressure and the number of particles). Raise from 10K to 200K took 90ns,then for 90ns systems were kept at 200K, then in 35ns the temperatures were risen to 309K.Afterwards 6Abeta 25-35 system was simulated for 95 ns of MD run at 309K.The multiple -sheet stack consisting of six 6Abeta 25-35 parallel -sheets (Figure 1)was built and subjected to 58 ns MD by similar protocol as that one for single -sheets. Thetemperature was risen stepwise from 10 K to 200 K during 31 ns, then the system were keptat 200 K for 18 ns, and then the temperature was risen to 309 K.Results and DiscussionResults of the single sheet MD of 6Abeta 25-35 and 10Abeta 25-35 show the stable -sheetacross the -sheet region from Ile31 to Leu 34. The -sheet region over region Ser26-Fig. 1. Hydrophobic core of 6A 25-35 stack ( -sheets I-VI). Ile31, Ile32- black, space fill.Leu34 – light gray, space fill. Met35 – dark gray, space fill.572