Prediction of Optimal Folding Routes of Proteins That Satisfy the Principle of Lowest Entropy Loss: Dynamic Contact Maps and Optimal Control

An optimization model is introduced in which proteins try to evade high energy regions of the folding landscape, and prefer low entropy loss routes during folding. We make use of the framework of optimal control whose convenient solution provides practical and useful insight into the sequence of events during folding. We assume that the native state is available. As the protein folds, it makes different set of contacts at different folding steps. The dynamic contact map is constructed from these contacts. The topology of the dynamic contact map changes during the course of folding and this information is utilized in the dynamic optimization model. The solution is obtained using the optimal control theory. We show that the optimal solution can be cast into the form of a Gaussian Network that governs the optimal folding dynamics. Simulation results on three examples (CI2, Sso7d and Villin) show that folding starts by the formation of local clusters. Non-local clusters generally require the formation of several local clusters. Non-local clusters form cooperatively and not sequentially. We also observe that the optimal controller prefers “zipping” or small loop closure steps during folding. The folding routes predicted by the proposed method bear strong resemblance to the results in the literature

Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle

Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1-dependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src inactivation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers

The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation

J.C.Y. was funded by an MRC PhD studentship. D.J.B. is supported by a London Research Institute, Cancer Research UK Postdoctoral Fellowship award and M.W. is supported by Cancer Research UK. K.A. was supported by the Deutsche Forschungsgemeinschaft (AK 6/22-1 and AK 6/22-2) and the Center for Biological Signaling Studies in Freiburg (Germany). This work was supported by grants from the Wellcome Trust to G.F. and S.J.M

A RISING g-factor measurement of the 19/2(+) isomer in Sn-127

The g-factor of the 19/2+T-1/2 = 4.5(3) mu s isomer in Sn-127, which was populated in relativistic projectile fragmentation, was measured within the g-RISING campaign at GSI, utilizing the time-differential perturbed angular distribution method. The deduced g-factor vertical bar g vertical bar approximate to 0.16 is in agreement with theoretical estimates based on the empirical g-factors. (c) 2007 Elsevier B.V. All rights reserved.status: publishe

g-factor measurements at RISING: The cases of Sn-127 and Sn-128

We report on g-factor measurements of the 19/2+ T1/2=4.5(3) μs isomer in 127Sn and the 10+ T1/2=2.69(23) μs isomer in 128Sn. These isomers were produced and spin-aligned in relativistic heavy-ion fragmentation at GSI and were selected and separated by the GSI fragment separator (FRS). The γ-rays of the isomeric decay were detected by the RISING γ-ray spectrometer. The method of time-differential perturbed angular distributions was utilized. The measured g-factors, g(19/2+; 127Sn)=− 0.17(2) and g(10+; 128Sn)=− 0.20(4), are compared with shell model calculations. The measured g-factors confirm the predominantly νh11/2− 2 and ν(s1/2− 1h11/2−2) character of the 10+ and 19/2− isomers in 128Sn and 127Sn, respectively. The results demonstrate the feasibility of the method for similar measurements in exotic neutron-rich nuclei

Quantum effects in spontaneous emission by a relativistic, undulating electron beam

Current models of the effect of spontaneous emission on the electron beam dynamics neglect the discreteness of electron recoil associated with photon emission. We present a novel, one-dimensional model of the effect of spontaneous emission on the electron beam dynamics in an undulator both in the classical regime where discrete electron recoil is negligible, and in the quantum regime where it is significant. It is shown that in the classical regime, continuous decrease of the average electron energy and diffusive growth of the electron energy spread occurs, in agreement with previous classical models. In the quantum regime, it is shown that the evolution of the electron momentum distribution occurs as discrete momentum groups according to a Poisson distribution. The narrow momentum features of the quantum regime may be useful for generation of coherent radiation, which relies on electron beams having sufficiently narrow momentum/energy distributions