Research Projects - Other

The nature of modern science is that it is ever-changing, energetically crossing boundaries heretofore defined by traditional areas of inquiry. Research at the Theoretical and Computational Biophysics group reflects this dynamic, with studies employing theoretical perspectives and methodological approaches or addressing topics that don't fall easily into one of the above categories. Included in this broad category are studies of a four-way DNA junction, the nuclear pore complex, gas transport in hydrogenase that may provide a source of renewable fuel, and other topics.

O2 pathways in trematode hemoglobin

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made with VMD

Globins are oxygen-storing proteins, vital to life. In our blood, hemoglobins carry oxygen from our lungs to every cell in our body. In our muscles, myoglobins keep reserves of oxygen to make sure it is available when needed. In some plants, leghemoglobins capture oxygen molecules that would otherwise be harmful to the production of ammonium necessary for the plant's survival. All these globins possess an iron-containig "heme", that grabs on to oxygen for a short time, and share the same protein architecture, despite large variations in their sequences. Since the heme group is buried inside a globin, scientists wondered how oxygen makes its way inside the protein to reach it. Exploring the motion and energetics of globins using the program NAMD researchers learned to gather data that permitted them to visualize, utilizing the VMD software, all the pathways taken by oxygen migrating inside whale myoglobin (see the Aug 2006 highlight and related publication). However, when the researchers turned their attention to the rest of the globin family to compute their oxygen pathways, they found, on their computational spelunking trip, something surprising. Given the conserved architecture of all globins, they expected to see similar oxygen pathways throughout the globin family, but they saw the opposite! Aside from a conserved pocket right at the heme binding site, the distribution of oxygen pathways showed very little similarity from one globin to the next. This result is described in a recent report, which shows that oxygen-pathways are not conserved by evolution, and that their location is not determined by a protein's overall architecture, but rather by its local amino acids. The researchers also learned which amino acids are found more often than others lining oxygen pathways, recognizing that bulky side groups are not hindering, but favoring oxygen passage. More information can be found here.

All Spotlights

Papers

Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Gongpu Zhao, Juan R. Perilla, Ernest L. Yufenyuy, Xin Meng, Bo Chen, Jiying Ning, Jinwoo Ahn, Angela M. Gronenborn, Klaus Schulten, Christopher Aiken, and Peijun Zhang. Nature, 497:643-646, 2013.

A computational kinetic model of diffusion for molecular systems. Ivan Teo and Klaus Schulten. Journal of Chemical Physics, 139:121929, 2013.

Effects of cytosine hydroxymethylation on DNA strand separation. Philip M.D. Severin, Xueqing Zou, Klaus Schulten, and Hermann E. Gaub. Biophysical Journal, 104:208-215, 2013.

DNA target sequence identification mechanism for dimer-active protein complexes. Markita P. Landry, Xueqing Zou, Lei Wang, Wai Mun Huang, Klaus Schulten, and Yann R. Chemla. Nucleic Acids Research, 41:2416-2427, 2013.

A computational kinetic model of diffusion for molecular systems. Ivan Teo and Klaus Schulten. Journal of Chemical Physics, 139:121929, 2013.

Decrypting cryptochrome: Revealing the molecular identity of the photoactivation reaction. Ilia A. Solov'yov, Tatiana Domratcheva, Abdul R. M. Shahi, and Klaus Schulten. Journal of the American Chemical Society, 134:18046-18052, 2012.

Further optimization of a hybrid united-atom and coarse-grained force field for folding simulations: Improved backbone hydration and interactions between charged side chains. Wei Han and Klaus Schulten. Journal of Chemical Theory and Computation, 8:4413-4424, 2012.

Molecular basis of drug resistance in A/H1N1 virus. Ariela Vergara-Jaque, Horacio Poblete, Eric Lee, Klaus Schulten, Fernando González-Nilo, and Christophe Chipot. Journal of Chemical Information and Modeling, 52:2650-2656, 2012.

Unique sugar-binding site mediates the distinct anti-influenza activity of pig surfactant protein D. Martin van Eijk, Michael J. Rynkiewicz, Mitchell R. White, Kevan L. Hartshorn, Xueqing Zou, Klaus Schulten, Dong Luo, Erika C. Crouch, Tanya M. Cafarella, James F. Head, Henk P. Haagsman, and Barbara A. Seaton. Journal of Biological Chemistry, 287:26666-26677, 2012.

High-performance scalable molecular dynamics simulations of a polarizable force field based on classical Drude oscillators in NAMD. Wei Jiang, David Hardy, James Phillips, Alex MacKerell, Klaus Schulten, and Benoit Roux. Journal of Physical Chemistry Letters, 2:87-92, 2011.

Probing a structural model of the nuclear pore complex channel through molecular dynamics. Lingling Miao and Klaus Schulten. Biophysical Journal, 98:1658-1667, 2010.

Flow-induced b-hairpin folding of the glycoprotein Iba b-switch. Xueqing Zou, Yanxin Liu, Zhongzhou Chen, Gloria Ines Cárdenas-Jirón, and Klaus Schulten. Biophysical Journal, 99:1182-1191, 2010.

Challenges in protein folding simulations. Peter L. Freddolino, Christopher B. Harrison, Yanxin Liu, and Klaus Schulten. Nature Physics, 6:751-758, 2010.

O2-reactivity of flavoproteins: Dynamic access of dioxygen to the active site and role of a H+ relay system in D-amino acid oxidase. Jan Saam, Elena Rosini, Gianluca Molla, Klaus Schulten, Loredano Pollegioni, and Sandro Ghisla. Journal of Biological Chemistry, 285:24439-24446, 2010.

Molecular dynamics simulations suggest that electrostatic funnel directs binding of Tamiflu to influenza N1 neuraminidases. Ly Le, Eric H. Lee, David J. Hardy, Thanh N. Truong, and Klaus Schulten. PLoS Computational Biology, 6:e1000939, 2010. (13 pages).

Limits for reduction of effective focal volume in multiple-beam light microscopy. Anton Arkhipov and Klaus Schulten. Optics Express, 17:2861-2870, 2009.

Transport-related structures and processes of the nuclear pore complex studied through molecular dynamics. Lingling Miao and Klaus Schulten. Structure, 17:449-459, 2009.

Double stranded DNA dissociates into single strands when dragged into a poor solvent. Shuxun Cui, Jin Yu, Ferdinand Kühner, Klaus Schulten, and Hermann E. Gaub. Journal of the American Chemical Society, 129:14710-14716, 2007.

Molecular dynamics simulations of the complete satellite tobacco mosaic virus. Peter L. Freddolino, Anton S. Arkhipov, Steven B. Larson, Alexander McPherson, and Klaus Schulten. Structure, 14:437-449, 2006.

Finding gas diffusion pathways in proteins: Application to O2 and H2 transport in CpI [FeFe]-hydrogenase and the role of packing defects. Jordi Cohen, Kwiseon Kim, Paul King, Michael Seibert, and Klaus Schulten. Structure, 13:1321-1329, 2005.

Binding dynamics of isolated nucleoporin repeat regions to importin-b. Timothy A. Isgro and Klaus Schulten. Structure, 13:1869-1879, 2005.

Conformational model of the Holliday junction transition deduced from molecular dynamics simulations. Jin Yu, Taekjip Ha, and Klaus Schulten. Nucleic Acids Research, 32:6683-6695, 2004.

Genetically engineered gold-binding polypeptides: Structure prediction and molecular dynamics. Rosemary Braun, Mehmet Sarikaya, and Klaus Schulten. Journal of Biomaterials Science, 13:747-758, 2002.