Bulletin of the American Physical Society
76th Annual Meeting of the Southeastern Section of APS
Volume 54, Number 16
Wednesday–Saturday, November 11–14, 2009; Atlanta, Georgia
Session PC: Computational Biophysics |
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Chair: Mukesh Dhamala, Georgia State University Room: Paris |
Saturday, November 14, 2009 10:45AM - 10:57AM |
PC.00001: Effect of mismatched base pair on transport properties of DNA Neranjan Edirisinghe, Vadym Apalkov Charge transport through DNA largely depends on the transfer integral between neighboring base pairs. Replacement of regular base pair with a mismatched base pair (mispair), such as G-A mispair, can change the transfer integral locally and hence can alter the charge transport properties. We investigate I-V characteristic of the DNA molecule of a finite length and its dependence on the position of the mispair within the chain and the type of conformation of the mispair using non-equilibrium Keldysh formalism. [Preview Abstract] |
Saturday, November 14, 2009 10:57AM - 11:09AM |
PC.00002: Accessing the limits of ab initio docking methods Radhey Shyam, Emil Alexov Ab initio protein docking is the prediction of the three dimensional structure of a protein-protein complex from the structures of two interacting proteins, receptor and ligand. Here we report our instigation of the performance of several popular ab initio docking algorithms (ZDOCK, GRAMM and 3D-Garden) in a bound test (lock-and-key) on very large set of 2903 cases taken from ProCom database. The bound test was preferred over the unbound because of two reasons (1) to test the performance of docking algorithms without obscuring the results with the effects originating from possible conformational changes and (2) to expand the benchmarking set since we do not need the 3D structures of isolated monomers. The assessment of the predictions was made by computing the ligand RMSD (L{\_}RMSD). The first ten ranked predictions were taken. It was found that, on average, only 28{\%} of the predictions resulted in L{\_}RMSD $<$ 10 A, which is the standard criterion of acceptable models in CAPRI. The performance of the methods was investigated with respect to physical characteristics of the receptor and ligand as well. [Preview Abstract] |
Saturday, November 14, 2009 11:09AM - 11:21AM |
PC.00003: Modeling Ionization Events iduced by Protein Protein Binding Rooplekha Mitra, Radhey Shyam, Emil Alexov The association of two or more biological macromolecules dramatically change the environment of the amino acids situated at binding interface and could change ionization states of titratable groups. The change of ionization due to the binding results in proton uptake/release and causes pH-dependence of the binding free energy. We apply computational method, as implemented in Multi Conformation Continuum Electrostatics (MCCE) algorithm, to study protonation evens on a large set of protein-protein complexes. Our results indicate that proton uptake/release is a common phenomena in protein binding since in vast majority of the cases (70{\%}) the binding caused at least 0.5 units proton change. The proton uptake/release was further investigated with respect to interfacial area and charges of the monomers and it was found that macroscopic characteristics are not important determinants. Instead, charge complementarity across the interface and the number of unpaired ionizable groups at the interface are the primary source of proton uptake/release. [Preview Abstract] |
Saturday, November 14, 2009 11:21AM - 11:33AM |
PC.00004: Multivariate Analysis of Conformational Changes Induced by Macromolecular Interactions Indranil Mitra, Emil Alexov Understanding protein-protein binding and associated conformational changes is critical for both understanding thermodynamics of protein interactions and successful drug discovery. Our study focuses on computational analysis of plausible correlations between induced conformational changes and set of biophysical characteristics of interacting monomers. It was done by comparing 3D structures of unbound and bound monomers to calculate the RMSD which is used as measure of the structural changed induced by the binding. We correlate RMSD with volumetric and interfacial charge of the monomers, the amino acid composition, the energy of binding, and type of amino acids at the interface. as predictors. The data set was analyzed with SVM in R {\&} SPSS which is trained on a combination of a new robust evolutionary conservation signal with the monomeric properties to predict the induced RMSD. The goal of this study is to undergo parametric tests and heirchiacal cluster and discriminant multivariate analysis to find key predictors which will be used to develop algorithm to predict the magnitude of conformational changes provided by the structure of interacting monomers. Results indicate that the most promising predictor is the net charge of the monomers, however, other parameters as the type of amino acids at the interface have significant contribution as well. [Preview Abstract] |
Saturday, November 14, 2009 11:33AM - 11:45AM |
PC.00005: Control of epileptiform bursting in the leech heart interneuron William Barnett, Martin Anquez, Torrey Harris, Gennady Cymbalyuk The network controlling heartbeat in the medicinal leech contains leech heart interneurons (HNs). We modeled them under specific pharmacological conditions. The Ca$^{2+}$ currents were blocked by Co$^{2+}$. The K$^{+}$ currents, apart from the non-inactivating current, I$_{K2}$, were blocked by 4AP. The hyperpolarization-activated current, I$_{h}$, was blocked by Cs$^{+}$. Under these conditions, epileptiform bursting characterized by long interburst intervals (IBI) has been shown. We considered three distinct cases. Model 1 included I$_{K2}$, I$_{h}$, and the fast Na$^{+}$ current, I$_{Na}$. Model 2 was characterized by I$_{Na}$, I$_{K2}$, and the persistent Na$^{+}$ current, I$_{NaP}$. Model 3 consisted of I$_{Na,}$ I$_{K2}$, I$_{h}$, and I$_{NaP}$. We also investigated the bi-stability of bursting and silence as the leak conductance, g$_{leak}$, was varied. We showed that in 1 and 3, model HNs demonstrated bi-stability of silence and bursting. We analyzed how IBI and burst duration are controlled by the manipulation of I$_{h}$ and I$_{NaP}$. In 1, as V$_{1/2}$ of I$_{h}$ decreased, IBI grew towards infinity one over the square root of the parameter difference. In 2, we showed that as g$_{NaP}$ decreased from 6.156 nS to 6.155 nS, IBI grew in accordance with the one over square root law. The system underwent a saddle-node bifurcation just below 6.155 nS. Supported by NSF PHY-0750456. [Preview Abstract] |
Saturday, November 14, 2009 11:45AM - 11:57AM |
PC.00006: The propensity to bi-stability of bursting and silence of the leech heart interneuron Tatiana Malaschenko, Diana Williams, Andrey Shilnikov, Gennady Cymbalyuk Bursting is one of primary activity regimes of neurons. Our previous study was focused on determining a generic biophysical mechanism underlying the transition between bursting and silence and the co-existence of these two regimes observed in a neuron model. We show that this co-existence can be explained by the unstable sub-threshold oscillations (USTO) separating silence and bursting. The range of the controlling parameters, where the co-existence is observed, is limited by the critical values of the system at which the Andronov-Hopf and homoclinic bifurcations occur. We investigate how different parameters of the model affect the width of the co-existence area. We study the effects of the variations of maximal conductances of every voltage-dependent current. The influence of each current was tested individually, one at the time. We found that only two of them had a significant effect on the range of co-existence. The increase of the maximal conductance of the hyperpolarization-activated cationic current I$_{h}$ would expand the area of co-existence. The decrease of the conductance of the LVA fast Ca$^{2+}$ current has the opposite effect. [Preview Abstract] |
Saturday, November 14, 2009 11:57AM - 12:09PM |
PC.00007: Computational Modeling of Molecular Effects of Mutations Causing Snyder-Robinson Syndrome Zhe Zhang, Shaolei Teng, Emil Alexov Snyder-Robinson syndrome is an X-linked mental retardation disorder disease. The disease is associated with defects in a particular biomolecule, the spermine synthase (SMS) protein. Specifically, three missense mutations, G56S, I150T and V132G in SMS were identified to cause the disease, but molecular mechanism of their effect is unknown. We apply single-point energy calculations, molecular dynamics simulations and pKa calculations to reveal the effects of these mutations on SMS's stability, flexibility and interactions. It is demonstrated that even saddle changes as very conservative mutations can significantly affect wild type properties of SMS protein. While the mutations do not involve ionizable groups, still slight changes in the protonation of neighboring amino acids are suggested by the computational protocol. The dynamics of SMS was also affected by the mutations resulting in larger structural fluctuations in the mutant protein compared to the wild type. At the same time, the effect on SMS's stability was found to depend on the location of the mutation site with respect to the surface of the protein. Our investigation suggests that the disease is caused by diverse molecular mechanisms depending on the site of mutation and amino acid type substitution. [Preview Abstract] |
Saturday, November 14, 2009 12:09PM - 12:21PM |
PC.00008: Resistive force theory for sand swimming Yang Ding, Ryan Maladen, Chen Li, Daniel Goldman We discuss a resistive force theory\footnote{Maladen et. al, Science, \textbf{325}, 314, 2009} that predicts the ratio of forward speed to wave speed (wave efficiency, $\eta$) of the sandfish lizard as it swims in granular media of varying volume fraction $\phi$ using a sinusoidal traveling wave body motion. In experiment $\eta\approx0.5$ independent of $\phi$ and is intermediate between $\eta \approx 0.2$ for low $Re$ Newtonian fluid undulatory swimmers like nematodes and $\eta \approx 0.9$ for undulatory locomotion on a deformable surface. To predict $\eta$ in granular media, we developed a resistive force model which balances thrust and drag force over the animal profile. We approximate the drag forces by measuring the force on a cylinder (a ``segment'' of the sandfish) oriented at different angles relative to the displacement direction. The model correctly predicts that $\eta$ is independent of $\phi$ because the ratio of thrust to drag is independent of $\phi$. The thrust component of the drag force is relatively larger in granular media than in low $Re$ fluids, which explains why $\eta$ in frictional granular media is greater than in viscous fluids. [Preview Abstract] |
Saturday, November 14, 2009 12:21PM - 12:33PM |
PC.00009: Dependency of Lipid Raft Diffusion on System Size Ryan Davis An inherit limitation in molecular dynamics is a finite system size. Although periodic boundary conditions can be used to mimic an infinite space, minimizing the artificial effects created by the physical dimensions of the system still remains an issue. Here I will discuss the undesirable relationship between system properties and system size observed via a dissipative particle dynamics approach. In particular, results illustrate a strong dependence between the diffusion of a lipid raft along a membrane and the length of the axis perpendicular to it, even at relatively large system sizes. Methods for obtaining system properties independently of simulation size are crucial for accurate results. [Preview Abstract] |
Saturday, November 14, 2009 12:33PM - 12:45PM |
PC.00010: Building phenomenological models of complex biological processes Bryan Daniels, Ilya Nemenman A central goal of any modeling effort is to make predictions regarding experimental conditions that have not yet been observed. Overly simple models will not be able to fit the original data well, but overly complex models are likely to overfit the data and thus produce bad predictions. Modern quantitative biology modeling efforts often err on the complexity side of this balance, using myriads of microscopic biochemical reaction processes with a priori unknown kinetic parameters to model relatively simple biological phenomena. In this work, we show how Bayesian model selection (which is mathematically similar to low temperature expansion in statistical physics) can be used to build coarse-grained, phenomenological models of complex dynamical biological processes, which have better predictive powers than microscopically correct, but poorely constrained mechanistic molecular models. We illustrate this on the example of a multiply-modifiable protein molecule, which is a simplified description of multiple biological systems, such as an immune receptors and an RNA polymerase complex. Our approach is similar in spirit to the phenomenological Landau expansion for the free energy in the theory of critical phenomena. [Preview Abstract] |
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