67 research outputs found
Simulations of HIV capsid protein dimerization reveal the effect of chemistry and topography on the mechanism of hydrophobic protein association
Recent work has shown that the hydrophobic protein surfaces in aqueous
solution sit near a drying transition. The tendency for these surfaces to expel
water from their vicinity leads to self assembly of macromolecular complexes.
In this article we show with a realistic model for a biologically pertinent
system how this phenomenon appears at the molecular level. We focus on the
association of the C-terminal domain (CA-C) of the human immunodeficiency virus
(HIV) capsid protein. By combining all-atom simulations with specialized
sampling techniques we measure the water density distribution during the
approach of two CA-C proteins as a function of separation and amino acid
sequence in the interfacial region. The simulations demonstrate that CA-C
protein-protein interactions sit at the edge of a dewetting transition and that
this mesoscopic manifestation of the underlying liquid-vapor phase transition
can be readily manipulated by biology or protein engineering to significantly
affect association behavior. While the wild type protein remains wet until
contact, we identify a set of in silico mutations, in which three hydrophilic
amino acids are replaced with nonpolar residues, that leads to dewetting prior
to association. The existence of dewetting depends on the size and relative
locations of substituted residues separated by nm length scales, indicating
long range cooperativity and a sensitivity to surface topography. These
observations identify important details which are missing from descriptions of
protein association based on buried hydrophobic surface area
3D Protein structure prediction with genetic tabu search algorithm
Abstract Background Protein structure prediction (PSP) has important applications in different fields, such as drug design, disease prediction, and so on. In protein structure prediction, there are two important issues. The first one is the design of the structure model and the second one is the design of the optimization technology. Because of the complexity of the realistic protein structure, the structure model adopted in this paper is a simplified model, which is called off-lattice AB model. After the structure model is assumed, optimization technology is needed for searching the best conformation of a protein sequence based on the assumed structure model. However, PSP is an NP-hard problem even if the simplest model is assumed. Thus, many algorithms have been developed to solve the global optimization problem. In this paper, a hybrid algorithm, which combines genetic algorithm (GA) and tabu search (TS) algorithm, is developed to complete this task. Results In order to develop an efficient optimization algorithm, several improved strategies are developed for the proposed genetic tabu search algorithm. The combined use of these strategies can improve the efficiency of the algorithm. In these strategies, tabu search introduced into the crossover and mutation operators can improve the local search capability, the adoption of variable population size strategy can maintain the diversity of the population, and the ranking selection strategy can improve the possibility of an individual with low energy value entering into next generation. Experiments are performed with Fibonacci sequences and real protein sequences. Experimental results show that the lowest energy obtained by the proposed GATS algorithm is lower than that obtained by previous methods. Conclusions The hybrid algorithm has the advantages from both genetic algorithm and tabu search algorithm. It makes use of the advantage of multiple search points in genetic algorithm, and can overcome poor hill-climbing capability in the conventional genetic algorithm by using the flexible memory functions of TS. Compared with some previous algorithms, GATS algorithm has better performance in global optimization and can predict 3D protein structure more effectively
Geometry and field theory in multi-fractional spacetime
We construct a theory of fields living on continuous geometries with
fractional Hausdorff and spectral dimensions, focussing on a flat background
analogous to Minkowski spacetime. After reviewing the properties of fractional
spaces with fixed dimension, presented in a companion paper, we generalize to a
multi-fractional scenario inspired by multi-fractal geometry, where the
dimension changes with the scale. This is related to the renormalization group
properties of fractional field theories, illustrated by the example of a scalar
field. Depending on the symmetries of the Lagrangian, one can define two
models. In one of them, the effective dimension flows from 2 in the ultraviolet
(UV) and geometry constrains the infrared limit to be four-dimensional. At the
UV critical value, the model is rendered power-counting renormalizable.
However, this is not the most fundamental regime. Compelling arguments of
fractal geometry require an extension of the fractional action measure to
complex order. In doing so, we obtain a hierarchy of scales characterizing
different geometric regimes. At very small scales, discrete symmetries emerge
and the notion of a continuous spacetime begins to blur, until one reaches a
fundamental scale and an ultra-microscopic fractal structure. This fine
hierarchy of geometries has implications for non-commutative theories and
discrete quantum gravity. In the latter case, the present model can be viewed
as a top-down realization of a quantum-discrete to classical-continuum
transition.Comment: 1+82 pages, 1 figure, 2 tables. v2-3: discussions clarified and
improved (especially section 4.5), typos corrected, references added; v4:
further typos correcte
The roots of romantic cognitivism:(post) Kantian intellectual intuition and the unity of creation and discovery
During the romantic period, various authors expressed the belief that through creativity, we can directly access truth. To modern ears, this claim sounds strange. In this paper, I attempt to render the position comprehensible, and to show how it came to seem plausible to the romantics. I begin by offering examples of this position as found in the work of the British romantics. Each thinks that the deepest knowledge can only be gained by an act of creativity. I suggest the belief should be seen in the context of the post-Kantian embrace of “intellectual intuition.” Unresolved tensions in Kant's philosophy had encouraged a belief that creation and discovery were not distinct categories. The post-Kantians held that in certain cases of knowledge (for Fichte, knowledge of self and world; for Schelling, knowledge of the Absolute) the distinction between discovering a truth and creating that truth dissolves. In this context, the cognitive role assigned to acts of creativity is not without its own appeal
Attraction to and Distancing of Visual Arts:The Eve of St. Agnes and Pre-Raphaelite Paintings
Flora's Go-betweens: Nectar, Insects, and Flowers in the Romantic Natural History of Pollination
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