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

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

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

4. XET+GLLX complex

5. XET+XXXGXXXG complex

7. 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

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

9. QM/MM MM Very fast Transferability problems No chemical reactions QMMM QMMM QM Accurate physics/chemistry Computer resource intensive 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 Interface ?

10. Hammerhead Ribozymes: A QM/MM study of the catalytic mechanism Methodology: (i)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 150 and 2’O-P < 3.25 Å. (ii) NAC transfered to QM/MM. Constrained dynamics along different reaction paths to study reaction. (1) (1) R.A. Torres and T.C. Bruice, J. Am. Chem. Soc. 122, 781 (2000).

11. Ion positions in the Domain V of a 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 Group II intron (1) R.K.O. Sigel and coworkers, Nature Struct. Biol. 7, 1111 (2000).