Nuance in the double-helix and its role in protein–DNA recognition

Abstract

It has been known for some time that the double-helix is not a uniform structure but rather exhibits sequence-specific variations that, combined with base-specific intermolecular interactions, offer the possibility of numerous modes of protein-DNA recognition. All-atom simulations have revealed mechanistic insights into the structural and energetic basis of various recognition mechanisms for a number of protein-DNA complexes while coarser grained simulations have begun to provide an understanding of the function of larger assemblies. Molecular simulations have also been applied to the prediction of transcription factor binding sites, while empirical approaches have been developed to predict nucleosome positioning. Studies that combine and integrate experimental, statistical and computational data offer the promise of rapid advances in our understanding of protein-DNA recognition mechanisms.

Sliding of p53 along DNA Can Be Modulated by Its Oligomeric State and by Cross-Talks between Its Constituent Domains

“…We assumed that the flexibility of DNA, which can have a major effect on the specific affinity of a protein for DNA, has a minor effect on nonspecific protein-DNA interactions. [82][83][84][85] The protein and the DNA were placed in a box with dimensions of 350 Å × 350 Å × 350 Å, with the DNA being placed at the center of the box along its z-axis.…”

Amino acids–nucleotides biomolecular recognition: from biological occurrence to affinity chromatography

“…In biological complexes it was already verified that the substitution of one single amino acid in the protein domain involved in recognition could induce a change on the DNA sequence that is recognized (Khorasanizadeh, 2004;Rohs et al, 2009). Although the bases' exposure is an important factor to determine the interaction with proteins, these complexes are stabilized for additional contacts between the lateral chains of amino acids and the deoxyribose rings and phosphate groups.…”

“…The possibility of numerous modes of protein-DNA recognition is related with some particularities of the nucleic acid molecule, such as its flexible structure, the presence of sequence-specific variations, combined with base-specific intermolecular interactions (Rohs et al, 2009). Unfortunately, the dependence of structure on sequence is not so well determined, since certain nucleotide sequences do not produce well-defined NMR maps.…”

“…Otherwise, an indirect model describes optimized protein-DNA interface geometries, taking account the global DNA structure influenced by the sequence-dependent bending (Rohs et al, 2009). In fact, these models have to be considered as simplified hypothesis to explain the complex mechanism underlined in the recognition and binding process involving these biomolecules.…”

Probing DNA shape and methylation state on a genomic scale with DNase I

“…An explanation for these phenomena might be found in the 3D structure of DNA (20). We recently showed that DNA shape plays an important role in protein-DNA recognition (21)(22)(23)(24).…”