Geometry of compact tubes and protein structures

Proteins form a very important class of polymers. In spite of major advances in the understanding of polymer science, the protein problem has remained largely unsolved. Here, we show that a polymer chain viewed as a tube not only captures the well-known characteristics of polymers and their phases but also provides a natural explanation for many of the key features of protein behavior. There are two natural length scales associated with a tube subject to compaction -- the thickness of the tube and the range of the attractive interactions. For short tubes, when these length scales become comparable, one obtains marginally compact structures, which are relatively few in number compared to those in the generic compact phase of polymers. The motifs associated with the structures in this new phase include helices, hairpins and sheets. We suggest that Nature has selected this phase for the structures of proteins because of its many advantages including the few candidate strucures, the ability to squeeze the water out from the hydrophobic core and the flexibility and versatility associated with being marginally compact. Our results provide a framework for understanding the common features of all proteins.Comment: 15 pages, 3 eps figure

Unified perspective on proteins: A physics approach

We study a physical system which, while devoid of the complexity one usually associates with proteins, nevertheless displays a remarkable array of protein-like properties. The constructive hypothesis that this striking resemblance is not accidental leads not only to a unified framework for understanding protein folding, amyloid formation and protein interactions but also has implications for natural selection.Comment: 26 pages, 15 figures, to appear on Phys. Rev.

Geometrical model for the native-state folds of proteins

We recently introduced a physical model [Hoang et al., P. Natl. Acad. Sci. USA (2004), Banavar et al., Phys. Rev. E (2004)] for proteins which incorporates, in an approximate manner, several key features such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and the role played by hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as broad competing minima in the free energy landscape even for a homopolymer. Here we show how the introduction of sequence heterogeneity using a simple scheme of just two types of amino acids, hydrophobic (H) and polar (P), and sequence design allows a selected putative native fold to become the free energy minimum at low temperature. The folding transition exhibits thermodynamic cooperativity, if one neglects the degeneracy between two different low energy conformations sharing the same fold topology.Comment: 12 pages, 3 figure

When a DNA Triple helix melts: An analog of the Efimov state

The base sequences of DNA contain the genetic code and to decode it a double helical DNA has to open its base pairs. Recent studies have shown that one can use a third strand to identify the base sequences without opening the double helix but by forming a triple helix. It is predicted here that such a three chain system exhibits the unusual behaviour of the existence of a three chain bound state in the absence of any two being bound. This phenomenon is analogous to the Efimov state in three particle quantum mechanics. A scaling theory is used to justify the Efimov connection. Real space renormalization group (RG), and exact numerical calculations are used to validate the prediction of a biological Efimov effect.Comment: Replaced by the (almost) published version, except the word "curiouser

Neural network time-series classifiers for gravitational-wave searches in single-detector periods

The search for gravitational-wave signals is limited by non-Gaussian transient noises that mimic astrophysical signals. Temporal coincidence between two or more detectors is used to mitigate contamination by these instrumental glitches. However, when a single detector is in operation, coincidence is impossible, and other strategies have to be used. We explore the possibility of using neural network classifiers and present the results obtained with three types of architectures: convolutional neural network, temporal convolutional network, and inception time. The last two architectures are specifically designed to process time-series data. The classifiers are trained on a month of data from the LIGO Livingston detector during the first observing run (O1) to identify data segments that include the signature of a binary black hole merger. Their performances are assessed and compared. We then apply trained classifiers to the remaining three months of O1 data, focusing specifically on single-detector times. The most promising candidate from our search is 2016-01-04 12:24:17 UTC. Although we are not able to constrain the significance of this event to the level conventionally followed in gravitational-wave searches, we show that the signal is compatible with the merger of two black holes with masses $m_1 = 50.7^{+10.4}_{-8.9}\,M_{\odot}$ and $m_2 = 24.4^{+20.2}_{-9.3}\,M_{\odot}$ at the luminosity distance of $d_L = 564^{+812}_{-338}\,\mathrm{Mpc}$.Comment: 29 pages, 11 figures, submitted to CQ

Structural motifs of biomolecules

Biomolecular structures are assemblies of emergent anisotropic building modules such as uniaxial helices or biaxial strands. We provide an approach to understanding a marginally compact phase of matter that is occupied by proteins and DNA. This phase, which is in some respects analogous to the liquid crystal phase for chain molecules, stabilizes a range of shapes that can be obtained by sequence-independent interactions occurring intra- and intermolecularly between polymeric molecules. We present a singularityfree self-interaction for a tube in the continuum limit and show that this results in the tube being positioned in the marginally compact phase. Our work provides a unified framework for understanding the building blocks of biomolecules.Comment: 13 pages, 5 figure

Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up

BACKGROUND: Intima-media thickness (IMT) is a validated marker of preclinical atherosclerosis and a predictor of cardiovascular events. PATIENTS: We studied a population of 529 asymptomatic patients (age 62\u2009\ub1\u200912.8 years), divided into two groups of subjects with and without Metabolic Syndrome (MetS). METHODS: All patients, at baseline, have had a carotid ultrasound evaluation and classified in two subgroups: the first one without atherosclerotic lesions and the second one with preclinical atherosclerosis (increased IMT or asymptomatic carotid plaque). Cardiovascular endpoints were investigated in a 20-years follow-up. RESULTS: There were 242 cardiovascular events: 144 among patients with MetS and 98 among in healthy controls (57.4% vs. 35.2%; P\u2009<\u20090.0001). 63 events occurred in patients with normal carotid arteries, while 179 events occurred in patients with preclinical atherosclerosis (31.8% vs. 54.1%; P\u2009<\u20090.0001). Of the 144 total events occurred in patients with MetS, 36 happened in the subgroup with normal carotid arteries and 108 in the subgroup with preclinical atherosclerosis (45% vs. 63.15%; P\u2009=\u20090.009). 98 events occurred in patients without MetS, of which 27 in the subgroup with normal carotid arteries and 71 in the subgroup with preclinical atherosclerosis (22.88% vs. 44.37%; P\u2009=\u20090.0003). In addition, considering the 63 total events occurred in patients without atherosclerotic lesions, 36 events were recorded in the subgroup with MetS and 27 events in the subgroup without MetS (45% vs. 22.88%; P\u2009=\u20090.0019). Finally, in 179 total events recorded in patients with preclinical carotid atherosclerosis, 108 happened in the subgroup with MetS and 71 happened in the subgroup without MetS (63.15% vs. 44.37%; P\u2009=\u20090.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P\u2009=\u20090.01, HR: 0.7366, CI: 0.5479 to 0.9904). CONCLUSIONS: Preclinical atherosclerosis leads to an increased risk of cardiovascular events, especially if it is associated with MetS