Biomedical relevance: Key result in 2011: Structure of ribosome-SecY- complex resolved by MDFF (TR&D3) 10 studies published by BTRC, e.g. Villa et al. PNAS (2009) 106:1063-1068. Seidelt et al. Science (2009) 326:1412-1415. Becker et al. Science (2009) 326:1369-1373. Frauenfeld et al. Nat. Struct. Mol. Biol. (2011) 18:614-621. Agirrezabala et al. PNAS (2012) In press. DBP 1: Structural analysis of ribosome by MDFF Hybrid tools to integrate multi-resolution structural data Frequent lack of complete crystallographic information require structure prediction tool Complex communication pathway (e.g. decoding) require efficient MD simulations to elucidate Computational challenges: Future studies include a) translational fidelity and b) nascent chain folding and localization. Over 50% of antibiotics target Many related diseases. e.g. Alzheimer’s disease due to dysfunctional ribosome (J. Neuroscience 2005, 25:9171-9175) Localization failure of nascent chain lead to neurodegenerative diseases (Mol. Bio. of the Cell 2005, 16:279-291) 13
4
Embed
DBP 1: Structural analysis of ribosome by MDFF · Mol. Biol. (2011) 18:614-621. Agirrezabala et al. PNAS (2012) In press. DBP 1: Structural analysis of ribosome by MDFF Hybrid tools
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Biomedical relevance: Key result in 2011: Structure of ribosome-SecY-complex resolved by MDFF (TR&D3)
10 studies published by BTRC, e.g.Villa et al. PNAS (2009) 106:1063-1068.Seidelt et al. Science (2009) 326:1412-1415.Becker et al. Science (2009) 326:1369-1373.Frauenfeld et al. Nat. Struct. Mol. Biol. (2011) 18:614-621.Agirrezabala et al. PNAS (2012) In press.
DBP 1: Structural analysis of ribosome by MDFF
Hybrid tools to integrate multi-resolution structural data
Frequent lack of complete crystallographic information require structure prediction tool
Complex communication pathway (e.g. decoding) require efficient MD simulations to elucidate
Computational challenges:
Future studies include a) translational fidelity and b) nascent chain folding and localization.
Over 50% of antibiotics target
Many related diseases. e.g. Alzheimer’s disease due to dysfunctional ribosome (J. Neuroscience 2005, 25:9171-9175)
Localization failure of nascent chain lead to neurodegenerative diseases (Mol. Bio. of the Cell 2005, 16:279-291)
Science (2009) x2, Nature Struct. Mol. Bio (2011),1 submitted
J. Mol. Bio. (2010), 1 submitted
New collaborator New collaborator
14
Chen et al. Submitted. Jan 2012.Collaboration with Taekjip Ha (UIUC)
Recent Progress 2: Ribosome assembly simulated by Go model
Chen et al. Submitted. Jan 2012.Collaboration with Taekjip Ha (UIUC)Collaboration with Taekjip Ha (UIUC)
Recent Progress 2: Ribosome assembly simulated by Go model
Simulations of five-way junction in ribosomal small subunit revealed pathways of binding of
ribosomal protein S4 that assists folding.
Recent Progress 3: Translational stalling by SecM
Gumbart et al. Submitted. Mar 2012.Collaboration with Roland Beckmann (U. Munich)
Simulations of MDFF-derived ribosome-SecM model revealed stalling mechanism that
up-regulates expression of SecA
Recent Progress 4: Structural characterization of mRNA-tRNA translocation intermediates. Agirrezabala et al. PNAS 2012. In press. Collaboration with Joachim Frank (Columbia U.)
Recent Progress 4: Structural characterization of mRNA-tRNA translocation intermediates. Agirrezabala et al. PNAS 2012. In press. PNAS 2012. In press. PNASCollaboration with Joachim Frank (Columbia U.)