arXiv subjects

Simcha Srebnik

Publications and source records attributed to Simcha Srebnik.

3 recordsLinked to original sources

arXiv2018

Unexpected water-hydroxide ion structure and diffusion behavior in low hydration media

Hydroxide ion transport and structure in aqueous media is fundamental to many chemical and biological processes. Research on hydroxide behavior has primarily focused on a single fully solvated hydroxide, either as an isolated cluster or in the bulk. This work presents the first computational study to consider a medium of low hydration levels where the hydroxide ion is microsolvated. Under such conditions, hydroxide ions are shown to be predominantly present as unique water-bridged double-hydroxide charged clusters, distinct from previously reported structures under hydrated conditions. Although layered double hydroxides were reported in the crystalline state, this is the first time to be seen in the disordered liquid state. These newly observed double-hydroxide structures presumably disrupt the hydrogen bonded network required for structural diffusion of hydroxide ions through water. These ion complexes have a higher ionic strength which may explain the unexpected diffusion behavior in comparison to the single hydroxide-water complex.

cond-mat.soft↗

arXiv2017

Assessment of hydrophobicity scales for protein stability and folding using energy and RMSD criteria

De novo prediction of protein folding is an open scientific challenge. Many folding models and force fields have been developed, yet all face difficulties converging to native conformations. Hydrophobicity scales (HSs) play a crucial role in such simulations as they define the energetic interactions between protein residues, thus determining the energetically favorable conformation. While many HSs have been developed over the years using various methods, it is surprising that the scales show very weak consensus in their assignment of hydrophobicity indexes to the various residues. In this work, several HSs are systematically assessed via atomistic Monte Carlo simulation of folding of small proteins, by converting the HSs of interest into residue-residue contact energy matrices. HSs that poorly preserve native structures of proteins were tuned by applying a linear transformation. Subsequently, folding simulations were used to examine the ability of the HSs to correctly fold the proteins from a random initial conformation. Root mean square deviation (RMSD) and energy of the proteins during folding were sampled and used to define an ER-score, as the correlation between the 2-dimensional energy-RMSD (ER) histogram with 50% lowest energy conformations and the ER histogram with 50% lowest RMSD conformations. Thus, we were able to compare the ability of the different HSs to predict de novo protein folding quantitatively.

q-bio.BM↗

arXiv2017

The Relation Between α-Helical Conformation And Amyloidogenicity

Amyloid fibrils are stable aggregates of misfolded proteins and polypeptides that are insoluble and resistant to protease activity. Abnormal formation of amyloid fibrils in vivo may lead to neurodegenerative disorders and other systemic amyloidosis such as Alzheimer's, Parkinson's, and atherosclerosis. Because of their clinical importance amyloids are found under intense scientific research. Amyloidogenic sequences of short polypeptide segments within proteins are responsible for the transformation of correctly folded proteins into parts of larger amyloid fibrils. The α-helical secondary structure is believed to host many amyloidogenic sequences and be a key player in different stages of the amyloidogenesis process. Most of the studies on amyloids focus on the role of amyloidogenic sequences. The focus of this study is the relation between amyloidogenicity and the structure of the amyloidogenic α-helical sequence. We have previously shown that the α-helical conformation may be expressed by two parameters (θ and \{rho}) that form orthogonal coordinates based on the Ramachandran dihedrals (ϕ and ψ) and provide an illuminating interpretation of the α-helical conformation. By performing statistical analysis on α-helical conformations found in the protein data bank, an apparent relation between α-helical conformation, as expressed by θ and \{rho}, and amyloidogenicity is revealed. Remarkably, random amino acid sequences, whose helical structure was obtained from the most probably dihedral angles as obtained from PDB data, revealed the same dependency of amyloidogenicity, suggesting the importance of α-helical structure as opposed to sequence.

q-bio.BM↗