The primitive data for deducing the Miyazawa-Jernigan contact energy or BLOSUM score metrix are the pair frequency counts. Each amino acid corresponds to a distribution. Taking the Kullback-Leibler distance of two probability distributions as resemblance coefficient and relating cluster to mixed population, we perform cluster analysis of amino acids based on the frequecy counts data. Furthermore, Ward's clustering is also obtained by adopting the average score as an objective function. An ordinal cophenetic is introduced to compare results from different clustering methods.
A mechanism for creating an enantioenrichment in the amino acids, the building blocks of the proteins, that involves global selection of one handedness by interactions between the amino acids and neutrinos from core-collapse supernovae is described. The chiral selection involves the dependence of the interaction cross sections on the orientations of the spins of the neutrinos and the 14N nuclei in the amino acids, or in precursor molecules, which in turn couple to the molecular chirality. It also requires an asymmetric distribution of neutrinos emitted from the supernova. The subsequent chemic…
The Supernova Neutrino Amino Acid Processing model, which uses electron anti-neutrinos and the magnetic field from a source object such as a supernova to selectively destroy one amino acid chirality, is studied for possible sites that would produce meteoroids having partially left-handed amino acids. Several sites appear to provide the requisite magnetic field intensities and electron anti-neutrino fluxes. These results have obvious implications for the origin of life on Earth.
Window profiles of amino acids in protein sequences are taken as a description of the amino acid environment. The relative entropy or Kullback-Leibler distance derived from profiles is used as a measure of dissimilarity for comparison of amino acids and secondary structure conformations. Distance matrices of amino acid pairs at different conformations are obtained, which display a non-negligible dependence of amino acid similarity on conformations. Based on the conformation specific distances clustering analysis for amino acids is conducted.
Group theoretical concepts are invoked in a specific model to explain how only twenty amino acids occur in nature out of a possible sixty four. The methods we use enable us to justify the occurrence of the recently discovered twenty first amino acid selenocysteine, and also enables us to predict the possible existence of two more, as yet undiscovered amino acids.
Using the crystal basis model of the genetic code, a set of relations between the physical-chemical properties of the amino acids are derived and compared with the experimental data. A prevision for the not yet measured thermodynamical parameters of three amino acids is done.
What are proteins made from, as the working parts of the living cells protein machines? To answer this question, we need a technology to disassemble proteins onto elementary func-tional details and to prepare lumped description of such details. This lumped description might have a multiple material realization (in amino acids). Our hypothesis is that informational approach to this problem is possible. We propose a way of hierarchical classification that makes the primary structure of protein maximally non-random. The first steps of the suggested research program are realized: the method and th…
A method is described where the aminoacyl-tRNA synthetase system is used to create very small devices for quantitative analysis of the amino acids that occur in proteins. The basis of the method is that each of the 20 synthetases and/or a tRNA specific for a different amino acid is separated spatially (e.g. in tiny chambers or on a surface). The reactions catalyzed by all 20 synthetases are monitored in a spatially resolved manner. Each separately positioned synthetase or tRNA will signal its cognate amino acid. The synthetase reactions can be monitored using continuous spectroscopic assays. A…
In this article, we have compared the metal-amino acid interactions in Tyr-Ag and Phe-Ag complexes through pH dependent SERS measurements. By analyzing the variation in relative intensities of SERS bands with the pH of the amino acid solution, we have obtained the orientation and conformation of the amino acid molecules on the Ag surface. The results obtained from our experimental studies are supported by the the energy minimized strucutres and the observed charge distributions in different terminals of the molecules. This, in a way, shows that SERS measurements not only exhibit the interactio…
Measurements of the isotopic abundances in meteoritic amino acids have found enhancements of $^2$H/H, $^{15}$N/$^{14}$N, and $^{13}$C/$^{12}$C in the amino acids in the meteorites studied. We show that they are consistent with the processing of the constituents of the meteorites by electron anti-neutrinos that would be expected from a core-collapse supernova or neutron-star merger. Using theoretical electron anti-neutrino cross sections we are able to predict these isotopic ratio variations depending on the time-integrated anti-neutrino flux at the site where the amino acids were processed.
Many commonly used force fields for protein systems such as AMBER, CHARMM, GROMACS, OPLS, and ECEPP have amino-acid-independent force-field parameters of main-chain torsion-energy terms. Here, we propose a new type of amino-acid-dependent torsion-energy terms in the force fields. As an example, we applied this approach to AMBER ff03 force field and determined new amino-acid-dependent parameters for $ψ$ and $ψ'$ angles for each amino acid by using our optimization method, which is one of the knowledge-based approach. In order to test the validity of the new force-field parameters, we then perfo…
The in silico design of peptides and proteins as binders is useful for diagnosis and therapeutics due to their low adverse effects and major specificity. To select the most promising candidates, a key matter is to understand their interactions with protein targets. In this work, we present PARCE, an open source Protocol for Amino acid Refinement through Computational Evolution that implements an advanced and promising method for the design of peptides and proteins. The protocol performs a random mutation in the binder sequence, then samples the bound conformations using molecular dynamics simu…
We report on the successful synthesis and hyperpolarization of N unprotected α amino acid ethyl acrylate esters and extensively, on an alanine derivative hyperpolarized by PHIP (4.4$\pm$1% $^{13}$C-polarization), meeting required levels for in vivo detection. Using water as solvent increases biocompatibility and the absence of N-protection is expected to maintain biological activity.
The primitive data for deducing the Miyazawa-Jernigan contact energy or BLOSUM score matrix consists of pair frequency counts. Each amino acid corresponds to a conditional probability distribution. Based on the deviation of such conditional probability from random background, a scheme for reduction of amino acid alphabet is proposed. It is observed that evident discrepancy exists between reduced alphabets obtained from raw data of the Miyazawa-Jernigan's and BLOSUM's residue pair counts. Taking homologous sequence database SCOP40 as a test set, we detect homology with the obtained coarse-grain…
The origin of chirality, closely related to the evolution of life on the earth, has long been debated. In 1991, Abdus Salam suggested a novel approach to achieve biomolecular homochirality by a phase transition. In his subsequent publication, he predicted that this phase transition could eventually change D-amino acids to L-amino acids as C -H bond would break and H atom became a superconductive atom. Since many experiments denied the configuration change in amino acids, Salam hypothesis aroused suspicion. This paper is aimed to provide direct experimental evidence of a phase transition in ala…
Amino acids in solar system bodies may have played a key role in the chemistry that led to the origin of life on Earth. We present laboratory studies testing the stability of amino acids against gamma radiation photolysis. All the 20 chiral amino acids in the levo form used in the proteins of the current terrestrial biochemistry have been irradiated in the solid state with gamma radiation to a dose of 3.2 MGy which is the dose equivalent to that derived by radionuclide decay in comets and asteroids in 1.05x109 years. For each amino acid the radiolysis degree and the radioracemization degree wa…
Using molecular dynamics simulations, the structure of model mini-protein was thoroughly characterized in the imidazolium-based amino acid ionic liquids and their aqueous solutions. We report that the mini-protein is more stable when AAIL is added as a cosolvent. Complete substitution of water by organic cations and anions further results in hindered conformational flexibility of the mini-protein. This observation suggests that AAILs are able to defend proteins from thermally induced denaturation. We show by means of radial distributions that the mini-protein is efficiently solvated by both so…
A mechanism for creating amino acid enantiomerism that always selects the same global chirality is identified, and subsequent chemical replication and galactic mixing that would populate the galaxy with the predominant species is described. This involves: (1) the spin of the 14N in the amino acids, or in precursor molecules from which amino acids might be formed, coupling to the chirality of the molecules; 2) the neutrinos emitted from the supernova, together with magnetic field from the nascent neutron star or black hole formed from the supernova selectively destroying one orientation of the …
The present study reports on the bio-organic composition of a deep-sea venting hydrothermal system originating from arc volcanism; the origin of the particulates in hydrothermal fluids from the Suiyo Seamount in the southern Izu-Bonin (Ogasawara) Arc is discussed with regard to amino compounds. Chimney samples on deep-sea hydrothermal systems and core samples at Suiyo Seamount were determined for amino acids, and occasionally amino sugars. Two types of chimney samples were obtained from active hydrothermal systems by submersible vehicles: one was natural chimney (NC) on a hydrothermal natural …
The previously formulated model for the evolution of the genetic code was shown to clarify why base triplets of some precursor amino acids differ by a single base from product amino acid codons, while others show less homology. First, the model indicated that the direction of code evolution changed on expansion from the N-fixers code (stage 2). Growth of the code from 16 codons in the NAN column (N, any standard nucleotide) proceeded by assignment of codons in the GNN, ANN, CNN and UNN rows. Expansion phase (stage 4 to 7) precursor/product pairs that spanned this shift included aspartate/threo…
How robust is the natural genetic code with respect to mistranslation errors? It has long been known that the genetic code is very efficient in limiting the effect of point mutation. A misread codon will commonly code either for the same amino acid or for a similar one in terms of its biochemical properties, so the structure and function of the coded protein remain relatively unaltered. Previous studies have attempted to address this question more quantitatively, namely by statistically estimating the fraction of randomly generated codes that do better than the genetic code regarding its overa…
Topological properties of native folds are obtained from statistical analysis of 160 low homology proteins covering the four structural classes. This is done analysing one, two and three-vertex joint distribution of quantities related to the corresponding network of amino acid residues. Emphasis on the amino acid residue hydrophobicity leads to the definition of their center of mass as vertices in this contact network model with interactions represented by edges. The network analysis helps us to interpret experimental results such as hydrophobic scales and fraction of buried accessible surface…
The discovery of amino acids in meteorites has presented two clues to the origin of their processing subsequent to their formation: a slight preference for left-handedness in some of them, and isotopic anomalies in some of their constituent atoms. In this article we present theoretical results from the Supernova Neutrino Amino Acid Processing (SNAAP) model, which uses electron anti-neutrinos and the magnetic fields from source objects such as supernovae or colliding neutron stars to selectively destroy one amino acid chirality and to create isotopic abundance shifts. For plausible magnetic fie…
Amino acids are considered to be prime ingredients in chemistry, leading to life. Glycine is the simplest amino acid and most commonly found in animal proteins. It is a glucogenic and non-essential amino acid that is produced naturally by living bodies and plays a key role in the creation of several other important bio-compounds and proteins. We report the first spectroscopic detection of the rotational absorption lines of the simplest amino acid glycine (NH$_{2}$CH$_{2}$COOH) with confirmer I and II in the atmosphere of Venus using the archival data from the Atacama Large Millimeter/Submillim…
The electrical properties of a set of seven-helix transmembrane proteins, whose space arrangement (3D structure) is known, are investigated by using regular arrays of the amino acids. These structures, specifically cubes, have topological features similar to those shown by the chosen proteins. The theoretical results show a good agreement between the predicted current-voltage characteristics obtained from a cubic array and those obtained from a detailed 3D structure. The agreement is confirmed by available experiments on bacteriorhodopsin. Furthermore, all the analyzed proteins are found to sh…
Efficient Proton Relay Orchestrated by Covalent Bond Switching of Active Amino Acids in Protein Channels
Nanjing University of Aeronautics and Astronautics（南京航空航天大学）；National Key Laboratory of Mechanics and Control for Aerospace Structures and Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, Institute for Frontier Science, Nanjing University of Aeronautics and Astronautics（航空航天结构力学与控制国家重点实验室与教育部智能纳米器件重点实验室前沿科学研究院，南京航空航天大学）；Max Planck–NTU Joint Lab for Artificial Senses, School of Materials Science and Engineering, Nanyang Technological University（南洋理工大学材料科学与工程学院马克斯·普朗克-南洋理工联合人工感觉实验室）；Nanyang Technological University（南洋理工大学）；School of Aerospace Engineering, Xi’an Jiaotong University（西安交通大学航天航空学院）
An In Silico model to relate the properties of proteins to the structure, sequence, function and evolutionary history of proteins is shown. The derived ideal sequences for amino acid residues in proteins can then be considered as attractors for structures of actual protein families and their functions. Hopfield networks1 can then act as GCMs (General Content Addressable Memories) when they are trained to recall unique pre-determined states when presented with information associated with that state. The tertiary structure of proteins is determined by structurally enforced interactions between r…
Extensive molecular dynamics simulations reveal that the interactions between proteins and poly(ethylene glycol)(PEG) can be described in terms of the surface composition of the proteins. PEG molecules accumulate around non-polar residues while avoiding polar ones. A solvent-accessible-surface-area model of protein adsorption on PEGylated nanoparticles accurately fits a large set of data on the composition of the protein corona recently obtained by label-free proteomic mass spectrometry.
The genetic code maps the sixty-four nucleotide triplets (codons) to twenty amino-acids. Some argue that the specific form of the code with its twenty amino-acids might be a 'frozen accident' because of the overwhelming effects of any further change. Others see it as a consequence of primordial biochemical pathways and their evolution. Here we examine a scenario in which evolution drives the emergence of a genetic code by selecting for an amino-acid map that minimizes the impact of errors. We treat the stochastic mapping of codons to amino-acids as a noisy information channel with a natural fi…
In this Communication we present statistical analysis of conservation profiles in families of homologous sequences for nine proteins whose folding nucleus was determined by protein engineering methods. We show that in all but one protein (AcP) folding nucleus residues are significantly more conserved than the rest of the protein. Two aspects of our study are especially important: 1) grouping of amino acids into classes according to their physical-chemical properties and 2) proper normalization of amino acid probabilities that reflects the fact that evolutionary pressure to conserve some amino …
Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic intera…
We seek to understand the interplay between amino acid sequence and local structure in proteins. Are some amino acids unique in their ability to fit harmoniously into certain local structures? What is the role of sequence in sculpting the putative native state folds from myriad possible conformations? In order to address these questions, we represent the local structure of each C-alpha atom of a protein by just two angles, theta and mu, and we analyze a set of more than 4000 protein structures from the PDB. We use a hierarchical clustering scheme to divide the 20 amino acids into six distinct …
