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Molecular Dynamics Simulations of DNA Double Helices: Studies of Sequence Dependence and the Role of Mismatch Pairs in the DNA Helix
Author(s) -
Rao Shashidhar N.,
Chandra Singh U.,
Kollman Peter A.
Publication year - 1986
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.198600028
Subject(s) - chemistry , molecular dynamics , helix (gastropod) , crystallography , dna , counterion , a dna , base pair , sequence (biology) , computational chemistry , ion , ecology , biochemistry , organic chemistry , snail , biology
We present the results of molecular dynamics simulations on base paired deoxyribonucleotides dA 10 ·dT 10 , d(GCGCGCGCGC) 2 d(ATATATATAT) 2 d(CGCGA)·d(TCACG) (AC mismatch) and d(CGAGA)·d(TCGCG) (GA mismatch). The average structural properties — helix parameters, H‐bond parameters, sugar puckers, torsional angles, root mean square atomic fluctuations — are compared to those found in earlier studies on the sequence d(CGCGA)·d(TCGCG). 1 The properties of the decamer helices remain B DNA like throughout the simulation, confirming our inference 1 that a model which treats solvent/counterions in a simple fashion (full charge on phosphates, but use of large hydrated counterions and a distance dependent dielectric constant) is a reasonable “first order” model to simulate the properties of DNA helices over periods of at least 100 psec. There are a number of sequence dependent effects observed in the three decanucleotides studied here, among them differences in H‐bond properties, sugar pucker and helix repeat/base tilts. In d(GCGCGCGCGC) 2 and d(ATATATATAT) 2 the H‐bonds all stay near the classic Watson‐Crick distance and the base tilts and twists are small (10–20°). On the other hand, in dA 10 ·dT 10 there are much larger deviations of H‐bonding from classic Watson‐Crick and H‐bond exchange during the simulation. There are many more examples of sugar repuckering in the AT decamers, and the relative frequency of such repuckering is qualitatively consistent with what one would expect based on molecular mechanics studies. A comparison of the torsional angles, sugar puckers, helical parameters, root mean square atom amplitudes and hydrogen bond parameters of the sequence d(CGCGA)·d(TCGCG) with the two mismatched analogues demonstrates that the effect of the poorer hydrogen bonding at the central base pair is transmitted throughout the sequence, leading to significantly greater root mean square fluctuations in all dihedral angles, significantly higher % of non‐“standard C2′ endo” sugar puckers, generally longer H‐bond distances, with greater % of “long” H bonds during the simulation, larger RMS amplitude of atomic fluctuations and greater helix twist and tilt of the base pairs. The average helix repeat is 9.0 for the AC mismatch, and 10.1 for the GA mismatch, compared to 10.0 for the normal sequence.