Descriptive statistics of disallowed regions and various protein secondary structures in the context of studying twisted β-hairpins

A detailed analysis of polypeptide-chain backbone conformations was carried out for polypeptide-chain segments adjacent to β-turn regions, including the sites of disallowed conformations. A cross comparison of conformations was performed for disallowed regions of the Ramachandran plot and main types of β-turns and adjacent secondary structures. Based on the results, disallowed region 2 (II, II') in the Ramachandran plot was shown to coincide mainly with β-hairpins and, more exactly, twisted β-hairpins. The frequency of residues with angles ?_i, ψ_i that fall in region 2 (II, II') in the latter is 140 times higher than in common β-hairpins.     

Predetermined Conformations in Bends of Polypeptide Chains: A Geometric Analysis

Biophysics - β-Bends are typical local structures of the polypeptide chain, are widespread in proteins, and play an important structural and functional role. It is possible to expect a priori...     

Noncanonical and Strongly Disallowed Conformations of the Backbone in Polypeptide Chains of Globular Proteins

An analog of the Ramachandran map was drawn, a new representation proposed, and thorough analysis performed using modern recognition and classification methods. Very large maps with a density of more than 50 million dots were created based on the data sets derived from the latest releases of globular protein- structure data banks. A, B, B', C, and D regions that correspond to strongly disallowed conformations were defined and found to occupy 25% of the plot area. A region of noncanonical conformations was determined by subtracting strongly disallowed and permitted conformation regions from the total plot area. Arguments are provided to support the new classification of backbone conformations of the protein polypeptide chain.     

A Long Short-Term Memory Neural Network Used to Predict the Exon–Intron Structure of a Gene

Biophysics - Several models of long short-term memory (LSTM) neural networks were constructed. Each model was trained on the complete mouse genome to predict the exon–intron structure of a...     

An Efficient Algorithm for Mapping of Reads to a Genome Graph Using an Index Based on Hash Tables and Dynamic Programming

The problem of storage of the sequences of a number of closely related genomes and analysis of genome variations is considered. A genome graph with the structure of an acyclic directed graph is used to store matching sections of sequences and known variants. An algorithm for rapid mapping of reads to the genome graph is developed to align the individual nucleotide sequence fragments to the genome graph. The algorithm combines rapid searching using hash tables with the algorithm of dynamic programming and solves the problem of exponential growth in the number of paths on the graph. The implementation of the genome graph and the algorithm of the alignment of reads is developed. A comparison with the best-known programs with similar functionality is made.     

The Conformational Stability/Lability of Peptide Fragments in the Sequence Context of Amino Acids

Biophysics - Criteria for evaluating the conformational stability/lability of peptide fragments referred to fragments of protein structures are formulated. Using the proposed criteria, a...     

Role of structural water for prediction of cation binding sites in apoproteins

Structures of many metal-binding proteins are often obtained without structural cations in their apoprotein forms. Missing cation coordinates are usually updated from structural templates constructed from many holoprotein structures. Such templates usually do not include structural water, the important contributor to the ion binding energy. Structural templates are also inconvenient for taking into account structural modifications around the binding site at apo-/holo- transitions. An approach based upon statistical potentials readily takes into account structural modifications associated with binding as well as contribution of structural water molecules. Here, we construct a set of statistical potentials for Mg²⁺, Ca²⁺, and Zn²⁺ contacting with protein atoms of a different type or structural water oxygens. Each type of the cations tends to form tight contacts with protein atoms of specific types. Structural water contributes relatively more into the binding pseudo-energy of Mg²⁺ and Ca²⁺ than of Zn²⁺. We have developed PIONCA (Protein-Ion Calculator), a fast CUDA GPGPU-based algorithm that predicts ion-binding sites in apoproteins. Comparative tests demonstrate that PIONCA outperforms most of the tools based on structural templates or docking. Our software can be also used for locating bound cations in holoprotein structures with missing cation heteroatoms. PIONCA is equipped with an interactive web interface based upon JSmol.     

The relationship between the sign of the polypeptide backbone angle omega and the type of the side chain radical of amino-acid residues

The dihedral angle ω, which reflects the nonplanarity of the peptide group, was found to be essential for describing the conformation of the polypeptide chain backbone in the context of particular side chain radicals of amino-acid residues. Conformational clusters corresponding to conformationally stable peptides identified previously were observed.