11,408 research outputs found
In silico prediction of mutant HIV-1 proteases cleaving a target sequence
HIV-1 protease represents an appealing system for directed enzyme re-design,
since it has various different endogenous targets, a relatively simple
structure and it is well studied. Recently Chaudhury and Gray (Structure (2009)
17: 1636 -- 1648) published a computational algorithm to discern the
specificity determining residues of HIV-1 protease. In this paper we present
two computational tools aimed at re-designing HIV-1 protease, derived from the
algorithm of Chaudhuri and Gray. First, we present an energy-only based
methodology to discriminate cleavable and non cleavable peptides for HIV-1
proteases, both wild type and mutant. Secondly, we show an algorithm we
developed to predict mutant HIV-1 proteases capable of cleaving a new target
substrate peptide, different from the natural targets of HIV-1 protease. The
obtained in silico mutant enzymes were analyzed in terms of cleavability and
specificity towards the target peptide using the energy-only methodology. We
found two mutant proteases as best candidates for specificity and cleavability
towards the target sequence
Covariant EBK quantization of the electromagnetic two-body problem
We discuss a method to transform the covariant Fokker action into an implicit
two-degree-of-freedom Hamiltonian for the electromagnetic two-body problem with
arbitrary masses. This dynamical system appeared 100 years ago and it was
popularized in the 1940's by the still incomplete Wheeler and Feynman program
to quantize it as a means to overcome the divergencies of perturbative QED. Our
finite-dimensional implicit Hamiltonian is closed and involves no series
expansions. The Hamiltonian formalism is then used to motivate an EBK
quantization based on the classical trajectories with a non-perturbative
formula that predicts energies free of infinities.Comment: 21 page
Structural Properties of the Disordered Spherical and other Mean Field Spin Models
We extend the approach of Aizenman, Sims and Starr for the SK-type models to
their spherical versions. Such an extension has already been performed for
diluted spin glasses. The factorization property of the optimal structures
found by Guerra for the SK model, which holds for diluted models as well, is
verified also in the case of spherical systems, with the due modifications.
Hence we show that there are some common structural features in various mean
field spin models. These similarities seem to be quite paradigmatic, and we
summarize the various techniques typically used to prove the structural
analogies and to tackle the computation of the free energy per spin in the
thermodynamic limit.Comment: 24 page
Long Range Magnetic Order and the Darwin Lagrangian
We simulate a finite system of confined electrons with inclusion of the
Darwin magnetic interaction in two- and three-dimensions. The lowest energy
states are located using the steepest descent quenching adapted for velocity
dependent potentials. Below a critical density the ground state is a static
Wigner lattice. For supercritical density the ground state has a non-zero
kinetic energy. The critical density decreases with for exponential
confinement but not for harmonic confinement. The lowest energy state also
depends on the confinement and dimension: an antiferromagnetic cluster forms
for harmonic confinement in two dimensions.Comment: 5 figure
A Computational Methodology to Screen Activities of Enzyme Variants
We present a fast computational method to efficiently screen enzyme activity.
In the presented method, the effect of mutations on the barrier height of an
enzyme-catalysed reaction can be computed within 24 hours on roughly 10
processors. The methodology is based on the PM6 and MOZYME methods as
implemented in MOPAC2009, and is tested on the first step of the amide
hydrolysis reaction catalyzed by Candida Antarctica lipase B (CalB) enzyme. The
barrier heights are estimated using adiabatic mapping and are shown to give
barrier heights to within 3kcal/mol of B3LYP/6-31G(d)//RHF/3-21G results for a
small model system. Relatively strict convergence criteria
(0.5kcal/(mol{\AA})), long NDDO cutoff distances within the MOZYME method
(15{\AA}) and single point evaluations using conventional PM6 are needed for
reliable results. The generation of mutant structure and subsequent setup of
the semiempirical calculations are automated so that the effect on barrier
heights can be estimated for hundreds of mutants in a matter of weeks using
high performance computing
Fractional-Spin Integrals of Motion for the Boundary Sine-Gordon Model at the Free Fermion Point
We construct integrals of motion (IM) for the sine-Gordon model with boundary
at the free Fermion point which correctly determine the boundary S matrix. The
algebra of these IM (``boundary quantum group'' at q=1) is a one-parameter
family of infinite-dimensional subalgebras of twisted affine sl(2). We also
propose the structure of the fractional-spin IM away from the free Fermion
point.Comment: 19 pages, LaTeX, no figure
Clustering of vertically constrained passive particles in homogeneous, isotropic turbulence
We analyze the dynamics of small particles vertically confined, by means of a
linear restoring force, to move within a horizontal fluid slab in a
three-dimensional (3D) homogeneous isotropic turbulent velocity field. The
model that we introduce and study is possibly the simplest description for the
dynamics of small aquatic organisms that, due to swimming, active regulation of
their buoyancy, or any other mechanism, maintain themselves in a shallow
horizontal layer below the free surface of oceans or lakes. By varying the
strength of the restoring force, we are able to control the thickness of the
fluid slab in which the particles can move. This allows us to analyze the
statistical features of the system over a wide range of conditions going from a
fully 3D incompressible flow (corresponding to the case of no confinement) to
the extremely confined case corresponding to a two-dimensional slice. The
background 3D turbulent velocity field is evolved by means of fully resolved
direct numerical simulations. Whenever some level of vertical confinement is
present, the particle trajectories deviate from that of fluid tracers and the
particles experience an effectively compressible velocity field. Here, we have
quantified the compressibility, the preferential concentration of the
particles, and the correlation dimension by changing the strength of the
restoring force. The main result is that there exists a particular value of the
force constant, corresponding to a mean slab depth approximately equal to a few
times the Kolmogorov length scale, that maximizes the clustering of the
particles
The way to ultrafast, high-throughput enantioseparations of bioactive compounds in liquid and supercritical fluid chromatography
Until less than 10 years ago, chiral separations were carried out with columns packed with 5 or 3 μm fully porous particles (FPPs). Times to resolve enantiomeric mixtures were easily larger than 30 min, or so. Pushed especially by stringent requirements from medicinal and pharmaceutical industries, during the last years the field of chiral separations by liquid chromatography has undergone what can be defined a “true revolution”. With the purpose of developing ever faster and efficient method of separations, indeed, very efficient particle formats, such as superficially porous particles (SPPs) or sub-2 μm FPPs, have been functionalized with chiral selectors and employed in ultrafast applications. Thanks to the use of short column (1–2 cm long), packed with these extremely efficient chiral stationary phases (CSPs), operated at very high flow rates (5–8 mL/min), resolution of racemates could be accomplished in very short time, in many cases less than 1 s in normal-, reversed-phase and HILIC conditions. These CSPs have been found to be particularly promising also to carry out high-throughput separations under supercritical fluid chromatography (SFC) conditions. The most important results that have been recently achieved in terms of ultrafast, high-throughput enantioseparations both in liquid and supercritical fluid chromatography with particular attention to the very important field of bioactive chiral compounds will be reviewed in this manuscript. Attention will be focused not only on the latest introduced CSPs and their applications, but also on instrumental modifications which are required in some cases in order to fully exploit the intrinsic potential of new generation chiral columns
Decision Problems For Convex Languages
In this paper we examine decision problems associated with various classes of
convex languages, studied by Ang and Brzozowski (under the name "continuous
languages"). We show that we can decide whether a given language L is prefix-,
suffix-, factor-, or subword-convex in polynomial time if L is represented by a
DFA, but that the problem is PSPACE-hard if L is represented by an NFA. In the
case that a regular language is not convex, we prove tight upper bounds on the
length of the shortest words demonstrating this fact, in terms of the number of
states of an accepting DFA. Similar results are proved for some subclasses of
convex languages: the prefix-, suffix-, factor-, and subword-closed languages,
and the prefix-, suffix-, factor-, and subword-free languages.Comment: preliminary version. This version corrected one typo in Section
2.1.1, line
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