生物物理学会サテライトミーティング

[CPS研究会]

2008年12月3−5日に福岡で開催される生物物理学会年会でサテライトミーティングを催しました。多数のご来場ありがとうございました。

 3M2 「計算タンパク質科学研究会」の紹介


11:45〜13:15 B会場 / Room B
代表: 高田彰二 (京都大学),由良 敬 (お茶の水女子大学)
Organizers: Shoji Takada (Kyoto Univ.) Kei Yura (Ochanomizu Univ.)

計算タンパク質科学研究会は、わが国におけるタンパク質立体構造を主眼とした計算生物学研究者交流を目指して、2005年に小さなグループで発足し、今年の9月にはオープン参加の会合を開催しました。今回のサテライトミーティングでは、研究会の活動紹介と当該分野の最新の研究報告を行います。
お弁当は配布されませんが、必要なら、各自持参してください

講演者(司会:高田彰二(京都大学))
11:45ー「計算タンパク質科学研究会の活動紹介」
        由良 敬(お茶の水女子大学) 
11:55− Protein Conformational Dynamics in Crystal Lattice 
        宮下 治 (アリゾナ大学) 
12:20− Unveiling conformational changes of biological molecules using multiscale modeling and multiresolution experiments
        Florence Tama (Univ Alizona) 
12:45− De novo computational design of "ideal" protein structure
        古賀信康、古賀(巽)理恵、David Baker (Washington Univ)
ーーー

ーー
3M2   Activity of Initiative for "Computational Protein Science (CPS)"

11:45 - 13:15  Room B
Organizers: Shoji Takada (Kyoto Univ.) Kei Yura (Ochanomizu Univ.)

Initiative for "Computational Protein Science (CPS)" was founded in 2005 without any official basis to promote computational/informational studies on protein structures amongst the next generation in Japan. The initiative held the fourth meeting last September this year. The activity of the initiative and the latest researches in the field will be presented in this satellite meeting.
Lunch box is not provided by organizers, but can be handed in by attendees.

Agenda (chaired by Shoij Takada (Kyoto Univ.))

 

  • 11:45- Introduction of the activity. Kei Yura (Ochanomizu Univ.)
  • 11:55- Protein Conformational Dynamics in Crystal Lattice. Osamu Miyashita (Univ. Arizona)
  • 12:20- Unveiling conformational changes of biological molecules using multiscale modeling and multiresolution experiments. Florence Tama (Univ. Arizona)
  • 12:45- De novo computational design of "ideal" protein structure. Nobuyasu Koga, Rie Tatsumi-Koga and David Baker (Washington Univ.) 


Abstracts

Protein Conformational Dynamics in Crystal Lattice

Osamu Miyashita
University of Arizona, Department of Biochemistry & Molecular Biophysics

Decades of investigation have confirmed the importance of protein dynamics to functions, and X-ray crystallography has been the most dominant source of information. It provides information on structure and dynamics of biological molecules, which are routinely used to discuss the structure/function relationship of proteins. However, such an interpretation is not straightforward. Proteins are flexible and take different conformations in solution, and there are many examples where different conformations of a protein were solved by X-ray crystallography. X-ray structures represent one snapshot of the conformational ensemble, which is selected by crystal packing. There is no standard approach to reconstruction of the ensemble in solution from X-ray structures. In this talk, I will present our recent studies to enhance our knowledge on protein structure and dynamics in crystal lattice to refine our interpretation of X-ray data to discuss protein structure/function relationship.

Unveiling conformational changes of biological molecules using multiscale modeling and multiresolution experiments

Florence Tama,
Department of Biochemistry & Molecular Biophysics, The University of Arizona,
1041 East Lowell Street - BSW 448, Tucson, AZ 85721

Multipronged approaches have recently gained interest for tackling structural problems related to large biological complexes. Structural dynamical information is often obtained by low-resolution experimental techniques, such as Cryo Electron Microscopy (cryo-EM), Small Angle X-ray Scattering (SAXS) and Fluorescence Resonance Energy 
Transfer (FRET). Each of these techniques offers different advantages and meet with different pitfalls, artifacts and limitations. Therefore a more accurate description could be obtained if all pieces of experimental data were taken together to annotate conformational states.
To achieve this goal we will present our current developments of multi-resolution/multi-scale computational tools to interpret conformational changes of biological molecules based on cryo-EM, SAXS or distance constraints. Normal Mode Analysis or Molecular Dynamics simulations are used to deform, in a physical manner, X-ray structures to fit low-resolution data. Using simulated data, we will show that such approaches are successful to predict structures in the range of 2~3 Å resolution.

De novo computational design of "ideal" protein structure

Nobuyasu Koga, Rie Tatsumi-Koga and David Baker
Dept. of Biochem., Univ of Washington

Computational design of an arbitrary structure from scratch provides a stringent test of our knowledge of protein folding, and allows us to determine the essential factors that lead to foldable sequences. Kuhlman et al., succeeded in designing the novel protein structure of Top7 by using Rosetta. However, it was observed that Top7 folds differently from other similarly sized naturally occurring proteins: Top7 exhibits non-native intermediates upon folding. These intermediates may be present because Top7 was designed by optimizing its sequence to stabilize the native structure, rather than optimizing the sequence in the context of the global energy landscape. This optimization strategy is unlikely to work for designing larger and more complicated structures because non-native intermediates can induce aggregation and prevent proper folding. Here, we explored a rational method of de novo structure design of alpha+beta proteins by explicitly designing sequences that have smooth funnel-like energy landscapes. Our results suggest that secondary structure (SS) length is an important parameter for de novo structure design. Optimal SS lengths eliminate non-native topologies by restricting the backbone structure, and producing smooth funnel-like energy landscapes. Moreover, we found a rule for selecting optimal SS lengths for creating alpha+beta proteins. By using optimized SS lengths, we were able to design an ideal structure of a ferredoxin-like fold, which was experimentally validated using CD spectrum and NMR.