of such subtle alterations did not result in a consistently disrupted hydrogen bonding network between simulation replicates that are 20 nanoseconds long. Therefore, longer such simulations in addition to simulations involving multiple modifications in parallel and those involving single bulky mutations are now being analyzed. Once suitable sets of modifications are predicted by MD simulation, the modified hairpin ribozymes will be chemically synthesized and kinetically characterized using single molecule fluorescence resonance en- ergy transfer together with functional analyses to dissect which kinetic steps, if any, are affected by disruption of the hydrogen bonding network. (1) Rhodes, M. M.; Reblova, K.; Sponer, J.; Walter, N. G. Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 13380-5. (2) Salter, J.; Krucinska, J.; Alam, S.; Grum-Tokars, V.; Wedekind, J. E. Biochemistry, 2006, 45, 686-700. 1710-Pos Board B602 How R-Proteins Stabilize the R-RNA during Early Stages of Bacterial Ribosome Biogenesis Jonathan Lai 1 , Ke Chen 1 , Hajin Kim 1 , Taejkip Ha 1 , Sarah Woodson 2 , Zan Luthey-Schulten 1 . 1 University of Illinois at Urbana-Champaign, Urbana, IL, USA, 2 Johns Hopkins University, Baltimore, MD, USA. Ribosome biogenesis in E. coli has been extensively studied, yet, very little is known about the structural changes that occur to the rRNA upon r-protein bind- ing. Recent cryo-electron microscopy and mass spectrometry studies from the Williamson laboratory have produced a time-resolved assembly map of the 16S subunit. The first r-protein to nucleate 16S folding, S4, binds to h16-h18 of the five-way junction–a signature region that idiosyncratically separates Bacteria and Archaea. S4, subsequently, nucleates the formation of the 5’ domain of the 16S and recruits other r-proteins to bind. Guided by in vitro studies, we probe how S4 nucleates the 5’ domain formation using a series of all-atom molecular dynamics (MD) simulations on the E. coli 5’ domain with various r-proteins systematically bound to the rRNA. Large dy- namic fluctuations in the structure of the rRNA were observed in both our long- time MD trajectories and multi-color single molecule FRET experiments from our collaborators. For example, with only S4 bound to the rRNA, an A-minor interaction between h8 and h14 opens up, but is stable upon adding S17 to a lo- cation distant from h8 and h14. We also are exploring the cooperative effects of the r-protein binding by gen- erating weighted networks based on position correlations. Graph of the network weighed by edge-betweenness, a measure of the number of shortest paths that pass through a given edge, show a continuous path connecting the binding sites of S4, S17, and S20 with a branching point located near h15–the binding site the secondary binding r-protein S16. This path is hypothesized to modulate the binding between primary and secondary binding r-proteins and further probed using additional all-atom and structure-based models. 1711-Pos Board B603 Aggregation of Therapeutic Antibodies: A Multiscale Molecular Dynamics Approach David R. Shorthouse, Mark S.P. Sansom. University of Oxford, Oxford, United Kingdom. The aggregation of proteins is a major challenge in the development of novel antibody based therapeutics. Therapeutic antibodies are produced and stored in extremely high concentrations and generated under varying and unfavoura- ble conditions for the stability of monomeric proteins. The aggregation of these proteins in solution can lead to serious consequences for patients in the form of the initiation of immune reactions, which have the potential to be fatal, and in the loss of clinical potency. Further to this, the type of aggregates formed by antibodies, and the processes that lead to their propagation, are relatively poorly understood. Thus by investigating these molecules as a model system we may find out more about other, more complex systems known to involve aggregation - including amyloids. Here we apply multiscale molecular dynamics simulations to investigate the aggregation of antibody fragments. using coarse-grained molecular dynamics (CG-MD) we are able to access much longer timescales than traditional atom- istic methodologies, and to look at much larger ensembles of proteins. Convert- ing back to atomistic detail then allows us to get a more detailed view of the interfaces between 2 proteins. CG simulations of systems containing 2 protein fragments give us insights into the specific interactions and, which surfaces on the molecular structures are in- volved in them. Simulations of much larger ensembles of proteins (from 4 and up to 16 antibody fragments) allow us to look the formation of larger aggregates, and can validate the surfaces discovered from simulations using only 2 fragments. Combining all these molecular dynamics methodologies we are able to gain in- sights into the most likely interactions between proteins, and on the most likely method of aggregation, and the potential structures of protein aggregates. 1712-Pos Board B604 Computational Modeling of a/b T-Cell Receptor Loop Conformations James Crooks, Ridgway Scott, Erin Adams. University of Chicago, Chicago, IL, USA. The T cell receptor plays a key role in the initiation of adaptive immune re- sponse by recognizing non-self peptides bound to MHC molecules. abTCRs engage peptide-MHC through six complementarity determining region (CDR) loops, three contributed by each of the alpha and beta chains. using these CDR loops, a single TCR can scan multiple MHC molecules and can also dis- tinguish self from non-self peptides bound in the MHC molecule. Upon engage- ment of a foreign MHC/peptide complex, a signaling cascade is initiated which eventually results in cytokine secretion or cytotoxicity of the target cell. Exper- imental data suggests that CDR loop conformations play a key role in this rec- ognition process. Crystallographic data has suggested that CDR loops have stereotyped positions, but the conformational space of the loops is poorly un- derstood, and in particular it is not well understood how the change in phase space of the loops contributes to the thermodynamics of peptide-MHC recog- nition. Here we have performed molecular dynamics simulations of the motions of bound and unbound TCR states and applied modern dimensional reduction and cluster analysis techniques to explore the number and size of CDR loop conformations. From this we have been able to explore the conformational and energetic landscape of the loop motions. 1713-Pos Board B605 Single-Stranded DNA within Nanopores: Conformational Dynamics and Implications for Sequencing; a Molecular Dynamics Simulation Study Syma Khalid, Andrew T. Guy. University of Southampton, UK, Southampton, United Kingdom. Engineered protein nanopores, such as those based on a-hemolysin from Staph- ylococcus aureus have shown great promise as components of next-generation DNA sequencing devices. However, before such protein nanopores can be used to their full potential, the conformational dynamics and translocation pathway of the DNA within them must be characterized at the individual molecule level. Here, we employ atomistic molecular dynamics simulations to study movement of single-stranded DNA through a simplified model of the a-hemolysin pore under an applied electric field. The simulations allow us to characterise the con- formations adopted by single-stranded DNA, and reveal how the conformations may impact on translocation within the wild-type model pore and a number of mutants. Our results show that specific interactions between the protein nano- pore and the DNA can have a significant impact on the DNA conformation of- ten leading to localized coiling, which in turn, can alter the order in which the DNA bases exit the nanopore. 1714-Pos Board B606 Towards Nanopore Sequencing: In-Silico Studies on the Interactions between Alpha-Hemolysin and SS DNA Molecules Suren Markosyan, Javier Eduardo Cuervo, Sergei Noskov. University of Calgary, Calgary, AB, Canada. Nanopore sequencing is a recently emerged approach and is an alternative to a classic and next generation genome sequencing techniques. Its main advan- tage over the others is the potential for achieving high-throughput sequencing with low material cost and high processing speed. On the basis of nanopore se- quencing technique are the interactions between a nanopore and a single stranded (ss) DNA molecule. Therefore better understanding of those interac- tions’ nature will greatly support the development of this new approach. In the current study we performed all-atom Molecular Dynamics (MD) simula- tions to examine the specific interactions of mutant alpha-hemolysin (aHl) nanopore with ss DNA, and Brownian Dynamics (Bromoc) simulations to mea- sure ion currents, to study long-time DNA dynamics and to test a specific case earlier reported in the literature. 1715-Pos Board B607 Molecular Dynamics Interactions between Silicon Electrodes and Phospholipids Zachary A. Levine 1,2 , Nadica Ivo sevic ´ DeNardis 3 , P. Thomas Vernier 2,4 . 1 Department of Physics and Astronomy, University of Southern California, Los Angeles, CA, USA, 2 MOSIS, Information Sciences Institute, Marina del Rey, CA, USA, 3 RuCer Bo skovi c Institute, Division for Marine and Environmental Research, Zagreb, Croatia, 4 Ming Hsieh Department of Electrical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA. In experiments involving the application of an external electric field to a biolog- ical system, the field is assumed to be uniform and isotropic far from the elec- trode interface, but adsorption of ions and molecules directly at the interface can complicate the structure of the charged double-layer. Reaction-kinetic models of lipid vesicle adhesion 1 have utilized continuum parameters such 334a Monday, February 4, 2013