Electrostatic Funneling of Nucleotide Binding in the Mitochondrial ADP/ATP Carrier Yi Wang, Biophysics and Computational Biology, UIUC The mitochondrial ADP/ATP carrier (AAC) is responsible for the exchange of ADP and ATP across the inner mitochondrial membrane. AAC switches between a cytoplasm-open state (c-state) and a matrix-open state (m-state) during nucleotide translocation. Although the structure of AAC in the c-state has been solved recently, the mechanism of nucleotide binding and the nature of conformational changes underlying the transition from the c-state to the m-state are not understood. Here we present over 300 ns molecular dynamics simulations on an AAC monomer embedded in a lipid bilayer. Our simulations reveal a strong positive electrostatic potential, induced by the heavily charged AAC, which is found to be crucial for nucleotide binding; further simulations with a biasing force reveal concerted outward rotation of the three odd-numbered helices of AAC, which opens the matrix half of the protein and allows for the translocation of the nucleotide. MRI-Based Finite Element Modeling of Mild Head Trauma: Part 1 - Imaging and Finite Element Mesh Generation Marcus Slavenas, Mechanical Science and Engineering, UIUC In order to perform simulations of the human head under impact loading, a finite element mesh was developed from a structural magnetic resonance image set. A T1 and a T2 weighted image were acquired from a single subject and co-registered for variation of head location within the scanner. FSL (a library of MRI analysis tools developed in Oxford, England) was used to produce a set of image files that designate each voxel as scalp, skull, cerebral spinal fluid (CSF), grey matter, white matter, or non-object. A C++ program was written that concatenates the image files, removes all non-object voxels, and creates a finite element mesh based upon the FSL tissue identification and the image geometry. The tissue geometry of the finite element mesh correlates well with the original image. The scalp thickness, skull thickness, and brain tissue segmentation are consistent with anatomy. Mesh smoothing and impact simulation are covered in Part 2. MRI-Based Finite Element Modeling of Mild Head Trauma: Part 2 - Mesh Smoothing and Simulation Results Ying Chen, Mechanical Science and Engineering, UIUC The present work describes the development of a patient-specific MRI-based three-dimensional finite element (FE) model of the human head. The FE mesh was generated from magnetic resonance imaging (MRI) scan data and this portion of the work was described in Part 1 of this talk. A smoothing technique was applied to the FE mesh to smooth the jagged edges on the outer surface and interfaces between two tissues without changing element connectivity. Material properties were taken from literature and assigned to each element according to the particular tissue type identified by the corresponding voxel intensity value of MRI scan data. Different materials considered in the current work were scalp, skull, cerebrospinal fluid, grey matter, and white matter. To validate the model, a frontal impact of human head was simulated using ABAQUS/Explicit. The numerical results were found to agree well with previous cadaver test data. The agreement indicates the potential use of the MRI-based finite element model for understanding mechanics of head trauma injuries. Measuring the distance of cargo from the microtubule for Kinesin Mlikhan Tanyeri,  Physics, UIUC Kinesin follows the microtubule protofilament axis. A microtubule can have different numbers of protofilaments (ranging from 10 to 19) in vitro depending on the buffer condition during polymerization. The protofilaments run parallel to the microtubule axis for a 13-protofilament; whereas they take a right-handed supertwist with a pitch of 3.4 micrometers for a 12-protofilament microtubule and a left-handed supertwist with a pitch of 6.8 micrometers for a 14-protofilament microtubule. We observed the motility of single Kinesin molecules on non-13 protofilament microtubules. Using the FIONA technique that our lab has established, we were able to localize Kinesin molecules with 1 nm accuracy. We have also developed a similar technique to localize the microtubules with 3 nm accuracy. We measured the distance of the cargo (QDot 655) at the tail domain to the microtubule to be roughly 40 nm for a Kinesin construct with 560 residues. By tracking the distance of the tail domain of the Kinesin molecules from the microtubule, we confirmed the helical motion that a single Kinesin molecule undergoes on a non-13 protofilament microtubule. Directed Evolution of Orthogonal Ligand Specificity in a Single Scaffold Michael McLachlan, Center for Biophysics and Computational Biology, UIUC We describe the creation and use of two orthogonal, highly ligand-sensitive ligand-receptor pairs for transcriptional control in eukaryotes. Both were generated from the ligand-binding domain (LBD) of the human estrogen receptor alpha, demonstrating the versatility of this scaffold. The first pair, DHB-7S, improves upon the ligand sensitivity toward 4,4'-dihydroxybenzil (DHB) of a previously engineered mutant, 4-S. The second ligand-receptor pair, L9-L7E, uses 2,4-di(4-hydroxyphenyl)-5-ethylthiazole (L9) as the target ligand.