Long-distance interactions and principles of molecular recognition at various biosystem organization levels

Efficient molecular recognition, in which recognition processes are occurring much faster than it takes to test variants, is only possible when long-distance recognition occurs together with contact interactions. The distance between interacting molecules should be sufficiently long to prevent hindrances to the search and, on the other hand, sufficiently short to provide selectivity. It was demonstrated that both of these two requirements can be satisfied simultaneously for biological macromolecules that include helical segments. Because the “diameters” of helical molecules are far shorter than their lengths, the intermolecular distance can be far greater than the diameters, thus allowing a free search. The distance can be far shorter than the lengths at the same time, thus providing selectivity. Analytical procedures were developed to estimate the parameters for protein–protein and protein–nucleic acid recognition. The coincidence of the charge-distribution periods in helical segments was found to substantially increase their interaction potential, and the reduction scale characteristic of the potential was shown to depend on the numerical value of the coinciding period.     

Mutual disposition of short conformationally stanch oligopeptides in the 3D structure of globular proteins

The disposition of conformationally stanch, helix-prone tetrapeptides and of longer segments containing them in proteins of different structural and functional groups (PDBselect and CATH samples) has been analyzed. Quasirandom Monte Carlo experiments show that the disposition of such segments can be regarded as stochastic. At that, ～60% of stanch peptides in the protein globules have at least one stanch neighbor within 5 Å.     

Classification of amino acids based on comparative analysis of contacts in DNA-protein complexes and specific DNA-protein interactions

We propose a classification of amino acid residues based on the events of contact formation between particular residues and DNA nucleotides, i.e., using the most integral properties that characterize interactions organizing DNA-protein complexes. We apply the Voronoi-Delaunay tessellation to draw statistics of contacts and of contact areas for a set of 1937 DNA-protein complexes. Similarity of amino acid residues is defined upon comparison of corresponding rows and matrices of contacts and areas of contacts. Nine measures of distance have been used to estimate the closeness of rows. Residues have been grouped by three hierarchical and two nonhierarchical clustering methods. In a total tree built using nine metrics with three hierarchical methods, we show that clustering centers (pairs of amino acids) in the main groups are always constant while other relationships between objects vary. Major classes of up to six amino acids correspond to certain local structures of the polypeptide chain. These data can be taken into account when designing DNA-protein ligands.     

Conformationally stable segments in helical structures of polypeptide chains of proteins and their role in high level structures formation

In the work the arguments are presented in favor of the idea on the role of conformationally stable oligopeptides in specific long-distance interactions in phenomena of molecular recognition during various biological processes. Original authors’ and literature data are taken into account. The examples of conformationally stable short oligopeptides participating in alpha-helix and collagen type structures formation are given simultaneously with theoretical approaches. The conformationally stable oligopeptides obtained in the course of PDB bank analysis are discussed. The role of amino acid sequence in collagen helix formation is shown.     

A Mathematical Approach that Includes the Fourier Transform (Plane Wave Decomposition Using Spherical Coordinates) and Simultaneously Assesses Complex Movements,Such as Rotations and Displacements,in Complicated Molecular Constructions

Biophysics - A multimodal mathematical approach is proposed that makes it possible to consider the Fourier objects that arise when macromolecules are described in spherical coordinates. With...     

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...     

On the optimal folding of protein molecules

The process of formation of a globular structure by a long molecular chain has been examined. In this process, various regions of the chain interact with one another. We classify the contacts thus formed as “correct” and “erroneous” ones. The correct contacts are those characteristic of the final native globular structure. All other contacts can be treated as erroneous. It is demonstrated that globule formation may proceed actually without formation and subsequent decay of erroneous contacts. Our model permits avoiding examination of numerous erroneous variants inasmuch as the regions of the chain that form correct contacts enter “long-range” interactions that at the same time can be highly selective. The existence of interactions of this kind facilitates the mutual approach and interaction of just those regions of the chain that yield correct contacts. Based on database analysis, it is shown that the model is valid not only for abstract structures but also for real polypeptide chains capable of forming protein globules and helical fibrils.     

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.     

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...     

Interconnection between the globule architecture and disposition of conformationally stanch oligopeptides in proteins of the same structural family

It has been shown that selective interactions between helical segments of macromolecules can be realized in globular proteins in the segments characterized by the same periodicities of charge distribution, i.e., conformationally stanch oligopeptides (CSOPs). It has been found that in the macromolecules of α-helical proteins, CSOPs are disposed at distances characteristic of direct interactions. For representatives of many structural families of α-type proteins, family-specific disposition of CSOPs is observed. The similar disposition of conformationally stanch segments is not related to amino acid sequence homology but reflects peculiarities of native 3D architectures of protein globules.