Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Statistical Thermodynamics of DNA Sequences Based on a Two State Model for the Base Pair Steps

A statistical thermodynamic framework is constructed for investigating the stability of DNA sequences and their potential for interaction with ligands and proteins, on the lines of structure based thermodynamics of Hilser and coworkers (1). Each base pair step (the dinucletotide) is considered to be either closed (as in the intact double helical DNA where in the Watson-Crick pairing and inter-strand and intra-strand stacking is intact; or open ( as in the locally molten state in which the Watson-Crick pairing and inter-strand stacking is completely lost and intra-strand stacking is partially disrupted). A sequence of n bases is characterized by n-1 base pair steps, leading to a total of 2(n-1) microstates which can be enumerated explicitly. The bp step free energies are adapted from experiment (2). This facilitates construction of the partition function and development of thermodynamic parameters as statistical mechanical ensemble averages over all the microstates. As an internal consistency check, the computed average free energies are plotted against experimental melting temperatures of 44 oligonucleotide sequences all at ~ 1M salt concentration, which gives a correlation coefficient of 0.89. The methodology has the potential to address questions concerning, sequence and stability, cooperativity in DNA-ligand/protein binding etc..


  1. V. J. Hilser, B. Garca-Moreno E., T. G. Oas, G. Kapp and S. T. Whitten, Chemical Reviews, 106(5), 1545-1558 (2006).
  2. J. SanataLucia Jr., PNAS, 95, 1460-1465 (1998).
  3. G. Khandelwal, R. A. Lee, B. Jayaram and D. L. Beveridge, (Manuscript in Preparation).

Garima Khandelwal1,2
Rebecca A. Lee2,4
B. Jayaram1,2,3
and David L. Beveridge4

1Department of Chemistry
2 Supercomputing Facility for Bioinformatics and Computational Biology
3School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India.
4Department of Chemistry and Molecular Biophysics Program
Wesleyan University, Middletown, CT-06459, USA

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