Bulletin of the American Physical Society
2007 APS March Meeting
Volume 52, Number 1
Monday–Friday, March 5–9, 2007; Denver, Colorado
Session A26: Focus Session: Protein Folding: Theory and Simulations I |
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Sponsoring Units: DCP DBP Chair: William Eaton, Laboratory of Chemical Physics, National Institutes of Health Room: Colorado Convention Center 205 |
Monday, March 5, 2007 8:00AM - 8:36AM |
A26.00001: Exploring The Folding Energy Landscape--Triumphs and Tribulations Invited Speaker: The folding process has become one of the best understood transformations of condensed matter,owing to the minimal frustration principle and the collective nature of the key bottlenecks in the folding process. I will discuss the limits of models based on topology alone and also highlight the effects of residual frustration and co-factors in some puzzling examples that challenge the funnel paradigm. [Preview Abstract] |
Monday, March 5, 2007 8:36AM - 9:12AM |
A26.00002: Simulating protein folding and aggregation on the 10 second timescale Invited Speaker: Understanding how proteins self-assemble or ``fold'' is a fundamental problem in biophysics. Moreover, the ability to understand and quantitatively predict folding kinetics would have many implications, especially in the area of diseases related to protein misfolding, such as Alzheimer's Disease. However, there are many challenges to simulating folding, most notably the great computational challenges of simulating protein folding with models with sufficient accuracy to make quantitative predictions of experiments. In my talk, I will discuss our recent work to combine distributed computing with a new theoretical technique (Markov State Models) in order to simulate folding on long timescales as well as the direct and quantitative experimental tests of these methods. I will conclude with the application of these methods to the study of the Abeta peptide, whose aggregation has been directly implicated as the toxic element in Alzheimer's Disease. [Preview Abstract] |
Monday, March 5, 2007 9:12AM - 9:48AM |
A26.00003: Understanding ensemble protein folding at atomic detail. Invited Speaker: Here we present a new all-atom model and development of simple potential functions (inspired by discoveries of general principles of protein folding) that allow to fold small proteins from sequence to near native structure at an atomic level of detail. Availability of numerous successful all-atom folding trajectories and their novel graph theoretical analysis, makes it possible to gain a detailed atomic level understanding of folding pathways/intermediates/transition states for engrailed homeodomain - a small alpha-helical protein that has been recently studied experimentally. [Preview Abstract] |
Monday, March 5, 2007 9:48AM - 10:00AM |
A26.00004: Investigating the Disordered States of Two Proteins Using Intramolecular Contact Formation Vijay Singh, Michaela Kopka, Yujie Chen, William Wedemeyer, Lisa Lapidus Using the quenching of the triplet state of tryptophan by cysteine, we investigate the unfolded states of two structurally similar but sequentially non-homologous proteins, the IgG binding domain of proteins L and G, under a range of denaturing conditions. These proteins show remarkably similar dynamics of intramolecular diffusion marked by a decrease in contact formation at denaturant conditions that favor folding. A reaction limited rate and the diffusion limited rate are obtained by measuring the viscosity dependence of the intramolecular contact rate. To further investigate the polymer dynamics of the unfolded state under folding conditions, we modeled the proteins as a worm-like chain with excluded volume using Szabo, Schulten and Schulten (SSS) theory to estimate the effective persistence length and intramolecular diffusion constant at various concentrations of GdnHCl. The results reveal an unfolded state under folding conditions that is significantly more compact and less diffusive than the fully denatured state. [Preview Abstract] |
Monday, March 5, 2007 10:00AM - 10:12AM |
A26.00005: Thermodynamics of the Beta-hairpin to Coil Transition using a Distance Constraint Model Oleg Vorov, Donald Jacobs, Dennis Livesay The configuration partition function is calculated exactly [1] for a distance constraint protein model that describes the beta-hairpin to coil transition. The model employs a Gaussian backbone chain of N atoms in which bonds may form to crosslink pairs of atoms in close proximity along the chain, represented by fluctuating distance constraints. Each distinct pattern of cross-linking bonds defines a constant energy over all atomic geometries that are consistent with the constraint topology. This geometrical degeneracy factor is directly calculated from configuration space integrals for each accessible constraint topology. All constraint topologies consistent with no pair of bonds that link two backbone atoms are themselves crossed are enumerated, leading to an analytical closed form expression for the configuration partition function. The phase diagram for the beta-hairpin to coil transition as a function of chain length has been studied. \newline \newline [1] O.K.Vorov, D.J.Jacobs, D.R.Livesay, subm. to Phys.Rev.Lett., 2006, in preparation. [Preview Abstract] |
Monday, March 5, 2007 10:12AM - 10:24AM |
A26.00006: ABSTRACT WITHDRAWN |
Monday, March 5, 2007 10:24AM - 10:36AM |
A26.00007: Lattice Model Investigations of Protein Aggregation Yanxin Liu, Prem Chapagain, Jose Parra, Bernard Gerstman Protein aggregation is known to be important in a variety of diseases. We have expanded a well-known 3-dimensional protein folding computer lattice model with explicit side-chains in order to investigate the thermodynamics and statistical mechanics of protein aggregation between two chains. The modeling of a two-chain system presents technical and physics issues in addition to those found when modeling only a single chain. We report on preliminary results of the simulations. [Preview Abstract] |
Monday, March 5, 2007 10:36AM - 10:48AM |
A26.00008: Effective potentials for Folding Proteins Chung-Yu Mou, Nan-Yow Chen, Zheng-Yao Su A coarse-grained off-lattice model that is not biased in any way to the native state is proposed to fold proteins. To predict the native structure in a reasonable time, the model has included the essential effects of water in an effective potential. Two new ingredients, the dipole-dipole interaction and the local hydrophobic interaction, are introduced and are shown to be as crucial as the hydrogen bonding. The model allows successful folding of the wild-type sequence of protein G and may have provided important hints to the study of protein folding. [Preview Abstract] |
Monday, March 5, 2007 10:48AM - 11:00AM |
A26.00009: Forced Unfolding of the Coiled-Coils of Fibrinogen by Single-Molecule AFM Andre Brown, Rustem Litvinov, Dennis Discher, John Weisel A blood clot needs to have the right degree of stiffness and plasticity for hemostasis, but the origin of these mechanical properties is unknown. Here we report the first measurements using single molecule atomic force microscopy (AFM) to study the forced unfolding of fibrinogen to begin addressing this problem. To generate longer reproducible curves than are possible using monomer, factor XIIIa cross-linked, single chain fibrinogen oligomers were used. When extended under force, these oligomers showed sawtooth shaped force-extension patterns characteristic of unfolding proteins with a peak-to-peak separation of approximately 26 nm, consistent with the independent unfolding of the coiled-coils. These results were then reproduced using a Monte Carlo simulation with parameters in the same range as those previously used for unfolding globular domains. In particular, we found that the refolding time was negligible on experimental time and force scales in contrast to previous work on simpler coiled-coils. We suggest that this difference may be due to fibrinogen's structurally and topologically more complex coiled-coils and that an interaction between the alpha C and central domains may be involved. These results suggest a new functional property of fibrinogen and that the coiled-coil is more than a passive structural element of this molecule. [Preview Abstract] |
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