220 research outputs found
Investigating the Molecular Basis of N-Substituted 1-Hydroxy-4-Sulfamoyl-2-Naphthoate Compounds Binding to Mcl1
Myeloid cell leukemia-1 (Mcl1) is an anti-apoptotic protein that has gained considerable attention due to its overexpression activity prevents cell death. Therefore, a potential inhibitor that specifically targets Mcl1 with higher binding affinity is necessary. Recently, a series of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoate compounds was reported that targets Mcl1, but its binding mechanism remains unexplored. Here, we attempted to explore the molecular mechanism of binding to Mcl1 using advanced computational approaches: pharmacophore-based 3D-QSAR, docking, and MD simulation. The selected pharmacophoreNNRRRyielded a statistically significant 3D-QSAR model containing high confidence scores (R-2 = 0.9209, Q(2) = 0.8459, and RMSE = 0.3473). The contour mapscomprising hydrogen bond donor, hydrophobic, negative ionic and electron withdrawal effectsfrom our 3D-QSAR model identified the favorable regions crucial for maximum activity. Furthermore, the external validation of the selected model using enrichment and decoys analysis reveals a high predictive power. Also, the screening capacity of the selected model had scores of 0.94, 0.90, and 8.26 from ROC, AUC, and RIE analysis, respectively. The molecular docking of the highly active compoundC40; 4-(N-benzyl-N-(4-(4-chloro-3,5-dimethylphenoxy) phenyl) sulfamoyl)-1-hydroxy-2-naphthoatepredicted the low-energy conformational pose, and the MD simulation revealed crucial details responsible for the molecular mechanism of binding with Mcl1
Thermalization from gauge/gravity duality: Evolution of singularities in unequal time correlators
We consider a gauge/gravity dual model of thermalization which consists of a
collapsing thin matter shell in asymptotically Anti-de Sitter space. A central
aspect of our model is to consider a shell moving at finite velocity as
determined by its equation of motion, rather than a quasi-static approximation
as considered previously in the literature. By applying a divergence matching
method, we obtain the evolution of singularities in the retarded unequal time
correlator , which probes different stages of the thermalization. We
find that the number of singularities decreases from a finite number to zero as
the gauge theory thermalizes. This may be interpreted as a sign of decoherence.
Moreover, in a second part of the paper, we show explicitly that the thermal
correlator is characterized by the existence of singularities in the complex
time plane. By studying a quasi-static state, we show the singularities at real
times originate from contributions of normal modes. We also investigate the
possibility of obtaining complex singularities from contributions of
quasi-normal modes.Comment: 35 pages, 4 figure
Mixed RG Flows and Hydrodynamics at Finite Holographic Screen
We consider quark-gluon plasma with chemical potential and study
renormalization group flows of transport coefficients in the framework of
gauge/gravity duality. We first study them using the flow equations and compare
the results with hydrodynamic results by calculating the Green functions on the
arbitrary slice. Two results match exactly. Transport coefficients at arbitrary
scale is ontained by calculating hydrodynamics Green functions. When either
momentum or charge vanishes, transport coefficients decouple from each other.Comment: 22 pages, 6 figure
Compactification on negatively curved manifolds
We show that string/M theory compactifications to maximally symmetric
space-times using manifolds whose scalar curvature is everywhere negative, must
have significant warping, large stringy corrections, or both.Comment: 18 pages, JHEP3.cl
Holographic dilepton production in a thermalizing plasma
We determine the out-of-equilibrium production rate of dileptons at rest in
strongly coupled N=4 Super Yang-Mills plasma using the AdS/CFT correspondence.
Thermalization is achieved via the gravitational collapse of a thin shell of
matter in AdS_5 space and the subsequent formation of a black hole, which we
describe in a quasistatic approximation. Prior to thermalization, the dilepton
spectral function is observed to oscillate as a function of frequency, but the
amplitude of the oscillations decreases when thermal equilibrium is approached.
At the same time, we follow the flow of the quasinormal spectrum of the
corresponding U(1) vector field towards its equilibrium limit.Comment: 21 pages, 7 figures. v2: Version accepted for publication in JHEP;
minor modifications, added reference
Pathologies in Asymptotically Lifshitz Spacetimes
There has been significant interest in the last several years in studying
possible gravitational duals, known as Lifshitz spacetimes, to anisotropically
scaling field theories by adding matter to distort the asymptotics of an AdS
spacetime. We point out that putative ground state for the most heavily studied
example of such a spacetime, that with a flat spatial section, suffers from a
naked singularity and further point out this singularity is not resolvable by
any known stringy effect. We review the reasons one might worry that
asymptotically Lifshitz spacetimes are unstable and employ the initial data
problem to study the stability of such systems. Rather surprisingly this
question, and even the initial value problem itself, for these spacetimes turns
out to generically not be well-posed. A generic normalizable state will evolve
in such a way to violate Lifshitz asymptotics in finite time. Conversely,
enforcing the desired asymptotics at all times puts strong restrictions not
just on the metric and fields in the asymptotic region but in the deep interior
as well. Generically, even perturbations of the matter field of compact support
are not compatible with the desired asymptotics.Comment: 36 pages, 1 figure, v2: Enhanced discussion of singularity, including
relationship to Gubser's conjecture and singularity in RG flow solution, plus
minor clarification
Holographic Brownian Motion in Magnetic Environments
Using the gauge/gravity correspondence, we study the dynamics of a heavy
quark in two strongly-coupled systems at finite temperature: Super-Yang-Mills
in the presence of a magnetic field and non-commutative Super-Yang-Mills. In
the former, our results agree qualitatively with the expected behavior from
weakly-coupled theories. In the latter, we propose a Langevin equation that
accounts for the effects of non-commutativity and we find new interesting
features. The equation resembles the structure of Brownian motion in the
presence of a magnetic field and implies that the fluctuations along
non-commutative directions are correlated. Moreover, our results show that the
viscosity is smaller than the commutative case and that the diffusion
properties of the quark are unaffected by non-commutativity. Finally, we
compute the random force autocorrelator and verify that the
fluctuation-dissipation theorem holds in the presence of non-commutativity.Comment: 34 pages. v2: typos corrected. v3: title and abstract slightly
modified in order to better reflect the contents of the paper; footnote 3 and
one reference were also added; version accepted for publication in JHE
Non-Perturbative Superpotentials in F-theory and String Duality
We use open-closed string duality between F-theory on K3xK3 and type II
strings on CY manifolds without branes to study non-perturbative
superpotentials in generalized flux compactifications. On the F-theory side we
obtain the full flux potential including D3-instanton contributions and show
that it leads to an explicit and simple realization of the three ingredients of
the KKLT model for stringy dS vacua. The D3-instanton contribution is highly
non-trivial, can be systematically computed including the determinant factors
and demonstrates that a particular flux lifts very effectively zero modes on
the instanton. On the closed string side, we propose a generalization of the
Gukov-Vafa-Witten superpotential for type II strings on generalized CY
manifolds, depending on all moduli multiplets.Comment: 49 pages, harvmac, 1 figure; references & figures adde
Shear Modes, Criticality and Extremal Black Holes
We consider a (2+1)-dimensional field theory, assumed to be holographically
dual to the extremal Reissner-Nordstrom AdS(4) black hole background, and
calculate the retarded correlators of charge (vector) current and
energy-momentum (tensor) operators at finite momentum and frequency. We show
that, similar to what was observed previously for the correlators of scalar and
spinor operators, these correlators exhibit emergent scaling behavior at low
frequency. We numerically compute the electromagnetic and gravitational
quasinormal frequencies (in the shear channel) of the extremal
Reissner-Nordstrom AdS(4) black hole corresponding to the spectrum of poles in
the retarded correlators. The picture that emerges is quite simple: there is a
branch cut along the negative imaginary frequency axis, and a series of
isolated poles corresponding to damped excitations. All of these poles are
always in the lower half complex frequency plane, indicating stability. We show
that this analytic structure can be understood as the proper limit of finite
temperature results as T is taken to zero holding the chemical potential fixed.Comment: 28 pages, 7 figures, added reference
Multi-scalar tachyon potential on non-BPS domain walls
We have considered the multi-scalar and multi-tachyon fields living on a 3d
domain wall embedded in a 5d dimensional Minkowski spacetime. The effective
action for such a domain wall can be found by integrating out the normal modes
as vibrating modes around the domain wall solution of a truncated 5d
supergravity action. The multi-scalar tachyon potential are good enough to
modeling assisted inflation scenario with multi-tachyon fields. The tachyon
condensation are also briefly addressed.Comment: version to appear in JHEP, 18 pages, 3 figure
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