Abstract
Background: Investigation of the specific protein-DNA complexation mechanisms allows to establish general principles of molecular recognition, which must be taken into account while developing artificial nanostructures based on DNA, and to improve the prediction efficiency of the protein binding sites on DNA. One of the main characteristics of the protein-DNA complexes are the number and type of contacts in the binding sites of DNA and proteins. Conformational changes in the DNA double helix can cause changes in these characteristics. Objectives: The purpose of our study is to establish the features of the interactions between nucleotides and amino acid residues in the binding sites of protein-DNA complexes and their dependence on the conformation of deoxyribose and the angle γ of the polynucleotide chain. Materials and methods: At research of protein-DNA recognition process we have analyzed the contacts between amino acids and nucleotides of the 128 protein-DNA complexes from the structural databases. Conformational parameters of DNA backbone were calculated using the 3DNA/CompDNA program. The number of contacts was determined using a geometric criterion. Two protein and DNA atoms were considered to be in contact if the distance between their centers is less than 4.5 A. Amino acid residues were arranged according to hydrophobicity scale as hydrophobic or nonpolar and polar. Results: The analysis of contacts between polar and hydrophobic residues and nucleotides with different conformations of the sugar-phosphate backbone showed that nucleotides form more contacts with polar amino acids in both grooves than with hydrophobic ones regardless of nucleotide conformation. But the profile of such contacts differs in minor and major grooves and depends on the conformation of both deoxyribose and γ angle. The contact profiles are characterized by the sequence-specificity or the different propensity of nucleotides to form contacts with the residues in both grooves. Conclusions: Our analysis have shown, that the amount and type of protein-nucleic contacts and their distribution in the grooves depend on the conformation of the sugar-phosphate backbone, the nucleotide sequence and the type of amino acids in the binding sites.
Highlights
Investigation of the specific protein-DNA complexation mechanisms allows to establish general principles of molecular recognition, which must be taken into account while developing artificial nanostructures based on DNA, and to improve the prediction efficiency of the protein binding sites on DNA
Prediction of protein binding sites on DNA will allow us to determine the functions of proteins and understand regulatory processes in molecular biological systems as well as to develop pharmaceutical drugs that can prevent the expression of target genes. For solving this problem some general principles concerning the frequency of formation of the specific amino acid-base pairs in binding sites should be formulated. In this investigation we try to identify common features of DNA backbone rearrangements which can effect on the ability of nucleotides to participate in contacts with proteins
The A-like nucleotides more often interact with proteins in the minor groove, while B-like nucleotides make more contacts in the major groove regardless of the γ angle conformation
Summary
Investigation of the specific protein-DNA complexation mechanisms allows to establish general principles of molecular recognition, which must be taken into account while developing artificial nanostructures based on DNA, and to improve the prediction efficiency of the protein binding sites on DNA. Objectives: The purpose of our study is to establish the features of the interactions between nucleotides and amino acid residues in the binding sites of protein-DNA complexes and their dependence on the conformation of deoxyribose and the angle γ of the polynucleotide chain. Results: The analysis of contacts between polar and hydrophobic residues and nucleotides with different conformations of the sugar-phosphate backbone showed that nucleotides form more contacts with polar amino acids in both grooves than with hydrophobic ones regardless of nucleotide conformation. Conclusions: Our analysis have shown, that the amount and type of protein-nucleic contacts and their distribution in the grooves depend on the conformation of the sugar-phosphate backbone, the nucleotide sequence and the type of amino acids in the binding sites.
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