Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data

and Computer Simulations

Poster Abstracts

113

78-POS

Board 38

Using the cgDNA Coarse-grain Model to Generate Sequence-dependent DNA

Configuration Ensembles

Daiva Petkeviciute

1,2

Ecole Polytechniqye Fédérale de Lausanne, Lausanne, Switzerland,

Kaunas University of

Technology, Kaunas, Lithuania.

The cgDNA coarse-grain model and its associated cgDNAmc Monte Carlo code [1, 2, 3] can

generate large equilibrium ensembles of configurations of naked B-DNA fragments in solution.

The appropriate length of such a fragment can vary from 10 to 10^4 base pairs, with any DNA

sequence being specified. For sequence length of 300 base pairs 1 million configurations can be

generated in approximately three minutes on a single processor [3]. The resulting ensembles are

strongly dependent on the sequence, e.g. as manifested in both the average shape and flexibility.

The model parameter sets are trained on libraries of Molecular Dynamics simulations, that are

many orders of magnitude more computationally demanding then the cgDNAmc code. At the

length scale of tens of bases model predictions can be compared with X-ray crystal structure and

NMR data, and the fits are shown to be in rather good agreement [2]. Another target application

of the model is estimating looping and cyclisation j factors [4]. Here we use the cgDNAmc to

study various notions of DNA persistence length [3].

[1] A sequence-dependent rigid-base model of DNA. O. Gonzalez, D. Petkevičiūtė, J. H.

Maddocks, J. Chem. Phys. 138 (5), 2013.

[2] cgDNA: a software package for the prediction of sequence-dependent coarse-grain free

energies of B-form DNA. D. Petkevičiūtė, M. Pasi, O. Gonzalez and J. H. Maddocks, Nucleic

Acids Res. 42 (20), 2014.

[3] Sequence-dependent persistence lengths of DNA. J. S. Mitchell, J. Glowacki, A. E.

Grandchamp, R. S. Manning and J. H. Maddocks, J. Chem. Theory Comput., 2016. DOI:

10.1021/acs.jctc.6b00904.

[4] DNA flexibility studied by covalent closure of short fragments into circles. D. Shore, J.

Langowski, R. L. Baldwin, Proc. Natl. Acad. Sci. USA 1981, 78, 4833–4837.