1 / 11

biotech.kth.se

Skolan för Bioteknologi. Biokemi (17). Träbioteknik (25). Bioprocess- teknologi (10). Teoretisk Kemi (52). Stefan Ståhl (Skolchef) 16 Professorer 90 Forskarstuderanden 44 Forskningsledare 215 Anställda. Genteknologi (30). Proteomik (45). Miljömikrobiologi (4). Nanobioteknologi (5).

dyan
Download Presentation

biotech.kth.se

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Skolan för Bioteknologi Biokemi (17) Träbioteknik (25) Bioprocess- teknologi (10) TeoretiskKemi (52) Stefan Ståhl (Skolchef) 16 Professorer90 Forskarstuderanden 44 Forskningsledare 215 Anställda Genteknologi (30) Proteomik (45) Miljömikrobiologi (4) Nanobioteknologi (5) www.biotech.kth.se Molekylär Bioteknik (30)

  2. Proteins in solution Proteins in solution Proteins targeting structures in vivo Proteins in cells

  3. Candida antarctica lipase B Lipase B from Candida antarctica is a serine hydrolase belonging to the a/b hydrolase family with a central b-sheet Surrounded by a-helixes The active site is deep in theproteinstructure Lipase B from Candida antarctica is very active and stable in most organic solvents

  4. XET+GLLX complex

  5. XET+XXXGXXXG complex

  6. VISION :3D Visualisation + Haptic Arms • Haptic arms for protein interaction and docking. 1 ns in real time – 10 ms in simulation time -- Coarse Grain Modeling

  7. MM part > 1000 solute atoms > 10000 solvent atoms Multiple Length Scales Interface region QM part ~ 100 atoms ~ 400 electrons  time evolution of a mixed QM/MM system. Galactose oxidase

  8. QMMM • Some bio-systems are very large • (too large for full QM) • and catalyse complicated reactions • (no force field available) • proteins >1000 atoms • solvent >10000 atoms • active site ~ 100 atoms QM/MM MM Very fast Transferability problems No chemical reactions QM Accurate physics/chemistry Computer resource intensive ? Interface

  9. Hammerhead Ribozymes: A QM/MM study of the catalytic mechanism • Methodology: • Classical (Amber98) MD simulations (3-4 ns). Previous theoretical studies (Torres and Bruice 2000) show Near Attack Conformations (NAC) in 18% of simulation time (1.2 ns).1 NAC: 2’O-P-5’O > 150 and 2’O-P < 3.25 Å. • (ii) NAC transfered to QM/MM. Constrained dynamics along different reaction paths to study reaction. (1) R.A. Torres and T.C. Bruice, J. Am. Chem. Soc. 122, 781 (2000).

  10. Ion positions in the Domain V of a group II intron Group II intron Highly conserved region of group II introns (ribozymes). DomainV plays critical role in excision (catalytic) activity. Bulge and loop regions seen to be metal-ion binding sites.1 Experimental difficulties in revealing metal-ion binding sites in helical stems I and II. Classical and QM/MM MD study of putative and crystallographic binding sites, and comparison with NMR/X-ray structures. Domain V (1) R.K.O. Sigel and coworkers, Nature Struct. Biol. 7, 1111 (2000).

More Related