Position-specific propensities of amino acids in the β-strand

<p>Abstract</p> <p>Background</p> <p>Despite the importance of <it>β</it>-strands as main building blocks in proteins, the propensity of amino acid in <it>β</it>-strands is not well-understood as it has been more difficult to determine experimentally compared to <it>α</it>-helices. Recent studies have shown that most of the amino acids have significantly high or low propensity towards both ends of <it>β</it>-strands. However, a comprehensive analysis of the sequence dependent amino acid propensities at positions between the ends of the <it>β</it>-strand has not been investigated.</p> <p>Results</p> <p>The propensities of the amino acids calculated from a large non-redundant database of proteins are found to be highly position-specific and vary continuously throughout the length of the <it>β</it>-strand. They follow an unexpected characteristic periodic pattern in inner positions with respect to the cap residues in both termini of <it>β</it>-strands; this periodic nature is markedly different from that of the <it>α</it>-helices with respect to the strength and pattern in periodicity. This periodicity is not only different for different amino acids but it also varies considerably for the amino acids belonging to the same physico-chemical group. Average hydrophobicity is also found to be periodic with respect to the positions from both termini of <it>β</it>-strands.</p> <p>Conclusions</p> <p>The results contradict the earlier perception of isotropic nature of amino acid propensities in the middle region of <it>β</it>-strands. These position-specific propensities should be of immense help in understanding the factors responsible for <it>β</it>-strand design and efficient prediction of <it>β</it>-strand structure in unknown proteins.</p

Probing Protein Shelf Lives from Inverse Mean First Passage Times

Protein aggregation is investigated theoretically via protein turnover, misfolding, aggregation and degradation. The Mean First Passage Time (MFPT) of aggregation is evaluated within the framework of Chemical Master Equation (CME) and pseudo first order kinetics with appropriate boundary conditions. The rate constants of aggregation of different proteins are calculated from the inverse MFPT, which show an excellent match with the experimentally reported rate constants and those extracted from the ThT/ThS fluorescence data. Protein aggregation is found to be practically independent of the number of contacts and the critical number of misfolded contacts. The age of appearance of aggregation-related diseases is obtained from the survival probability and the MFPT results, which matches with those reported in the literature. The calculated survival probability is in good agreement with the only available clinical data for Parkinson’s disease.<br /

Hydration Water Distribution around Intrinsically Disordered Proteins

The distribution and local structural order of hydration water in the proximity of intrinsically disordered proteins/regions are investigated within the frame work of three-dimensional (3D)-reference interaction site model theory. The hydration water distribution around the protein surface is quantified in terms of the 3D distribution function and the water–protein radial distribution function (RDF), whereas the local ordering of water molecules around the protein surface is measured in terms of the tetrahedral order parameter. To the best of our knowledge, this is the first theoretical study of the 3D hydration water distribution profiles of disordered proteins. The analysis of the 3D hydration profiles reveals a nonuniform distribution and higher hydration water density around disordered proteins as compared to the globular ones because of their noncompact structures with more solvent-accessible surface area and the abundance of charged residues. This difference is also evident in the residue-specific RDFs of water around different polar and nonpolar atoms of charged and hydrophobic residues of the globular and disordered proteins. The average tetrahedral order parameter evaluated as a function of the water–water distance shows that water molecules are more ordered around disordered regions/proteins because of their higher mean net charge facilitating stronger water–protein interactions

Dynamics of Fractional Brownian Walks

We investigate the dynamics of polymers whose solution configurations are represented by fractional Brownian walks. The calculation of the two dynamical quantities considered here, the longest relaxation time tau(r) and the intrinsic viscosity [eta], is formulated in terms of Langevin equations and is carried out within the continuum approach developed in an earlier paper. Our results for tau(r) and [eta] reproduce known scaling relations and provide reasonable numerical estimates of scaling amplitudes. The possible relevance of the work to the study of globular proteins and other compact polymeric phases is discussed

Chain dimensions near the critical point

We calculate the average end-to-end distance $\langle R^2\rangle$ of a polymer in a semidilute solution that is near the temperature $T_c$ at which phase separation occurs. The calculation is carried out within the usual canonical partition function formalism, the Hamiltonian of the system being taken to comprise a reference term, in which the chains are represented as collapsed coils, and a pertur- bation, which originates in repulsive excluded volume interactions between different monomers. The description of the reference state employs the fractional Brownian walk approach developed in an earlier paper, while the perturbation is modeled by delta function pseudopotentials. The treatment of excluded volume follows the methods developed by Edwards, Singh, and Jeffers, which make use of the equations derived for an effective step length and an effective monomer-monomer potential to determine various polymer properties. In this way, we find that near $T_c,$ R scales with chain length N as $N^{0.462}$

Radial dimensions of starburst polymers

Radial properties of starburst polymers are calculated by renormalization group techniques starting from the Edwards model of the chain. The calculations are carried out for a polymer in good solvents grown out to an arbitrary number of generations g and having an arbitrary branch functionality f. Excludd volume effects are modeled by delta function pseudopotentials. Only pair interactions are included in the calculations, which specifically determine the amplitude of the average center-to-end distance R of the starburst for definite values of f and g. Our first order in E estimates of the exponents for R and the number of configurations C coincide with results obtained earlier by direct methods for networks of arbitrary topology in specific limits

Local Order and Mobility of Water Molecules around Ambivalent Helices

Water on a protein surface plays a key role in determining the structure and dynamics of proteins. Compared to the properties of bulk water, many aspects of the structure and dynamics of the water surrounding the proteins are less understood. It is interesting therefore to explore how the properties of the water within the solvation shell around the peptide molecule depend on its specific secondary structure. In this work we investigate the orientational order and residence times of the water molecules to characterize the structure, energetics, and dynamics of the hydration shell water around ambivalent peptides. Ambivalent sequences are identical sequences which display multiple secondary structures in different proteins. Molecular dynamics simulations of representative proteins containing variable helix, variable nonhelix, and conserved helix are also used to explore the local structure and mobility of water molecules in their vicinity. The results, for the first time, depict a different water distribution pattern around the conserved and variable helices. The water molecules surrounding the helical segments in variable helices are found to possess a less locally ordered structure compared to those around their corresponding nonhelical counterparts and conserved helices. The long conserved helices exhibit extremely high local residence times compared to the helical conformations of the variable helices, whereas the residence times of the nonhelical conformations of the variable helices are comparable to those of the short conserved helices. This differential pattern of the structure and dynamics of water molecules in the vicinity of conserved/variable helices may lend valuable insights for understanding the role of solvent effects in determining sequence ambivalency and help in improving the accuracy of water models used in the simulations of proteins