ADAPT: A molecular mechanics approach for studying the structural properties of long DNA sequences

• Published in: BIOPOLYM. NUCLEIC ACID SCI. SECT 2000, Vol.56 (4), p.292-310
• Main Authors: Lafontaine, Ingrid, Lavery, Richard
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Base Sequence; Biochemistry, Molecular Biology; Computer Simulation; DNA; DNA - chemistry; DNA-Binding Proteins - metabolism; DNA-protein binding; Genes; Genome; genome analysis; Humans; Life Sciences; Ligands; Models, Molecular; Molecular dynamics; molecular modeling; Molecular structure; multicopy algorithm; Netropsin - metabolism; Nucleic Acid Conformation; Protein Binding; Proteins; sequence-structure relationships; TATA-Box Binding Protein; Thermodynamics; Transcription Factors - metabolism
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/1097-0282(2000)56:4<292::AID-BIP10028>3.0.CO;2-9

We describe an original approach to determining sequence–structure relationships for DNA. This approach, termed ADAPT, combines all‐atom molecular mechanics with a multicopy algorithm to build nucleotides that contain all four standard bases in variable proportions. These nucleotides enable us to search very rapidly for base sequences that energetically favor chosen types of DNA deformation or chosen DNA–protein or DNA–ligand interactions. Sequences satisfying the chosen criteria can be found by energy minimization, combinatorial sequence searching, or genome scanning, in a manner similar to the threading approaches developed for protein structure prediction. In the latter case, we are able to analyze roughly 2000 base pairs per second. Applications of the method to DNA allomorphic transitions, DNA deformation, and specific DNA interactions are presented. © 2001 John Wiley & Sons, Inc. Biopolymers (Nucleic Acid Sci) 56: 292–310, 2001