High-speed Molecular Mechanics Searches for Optimal DNA Interaction Sites

Authors: Lafontaine I.; Lavery R.

Source: Combinatorial Chemistry & High Throughput Screening, Volume 4, Number 8, December 2001 , pp. 707-717(12)

Publisher: Bentham Science Publishers

Abstract:

We have recently developed a theoretical means of studying the mechanical and interaction properties of nucleic acids as a function of their base sequence. This approach, termed ADAPT, can be used to obtain the physical properties of millions of base sequences with only modest computational expense. ADAPT is based on a multi-copy algorithm using special nucleotides (“lexides”) containing all four standard bases whose contribution to the energy of the molecule can be varied. We present here a deeper study of the energy minima which occur in the multi-dimensional space defined by these variable sequences. We also present an extension of the approach termed “gene threading” which enables us to scan genomic sequence data in an attempt to locate preferential binding sites. This technique is illustrated for the case of TATA-box protein binding. ADAPT enables us to demonstrate that, for this protein, DNA deformation alone explains a large part of the experimentally observed consensus binding sequence.

Keywords: Molecular Mechanics; Adapt; Protein dna recognition; Deformation energy; Multi copy algorithm; Genome analysis; Jumna; Dihydrofolate reductase

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1386207013330698

Publication date: 2001-12-01

• Combinatorial Chemistry & High Throughput Screening publishes full length original research articles and reviews describing various topics in combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) and/or high throughput screening (e.g. developmental, practical or theoretical). Ancillary subjects of key importance, such as robotics and informatics, will also be covered by the journal. In these respective subject areas, Combinatorial Chemistry & High Throughput Screening is intended to function as the most comprehensive and up-to-date medium available. The journal should be of value to individuals engaged in the process of drug discoveryand development, in the settings of industry, academia or government.

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