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DNA Binding Dynamics and Energetics of Cobalt, Nickel, and Copper Metallopeptides
Author(s) -
GalindoMurillo Rodrigo,
Cheatham Thomas E.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402020
Subject(s) - dodecameric protein , chemistry , atoms in molecules , dna , crystallography , energetics , molecule , nickel , molecular dynamics , thymine , density functional theory , ligand (biochemistry) , computational chemistry , stereochemistry , thermodynamics , biochemistry , physics , organic chemistry , receptor
We present molecular dynamics (MD) and Quantum Theory of Atoms in Molecules (QTAIM) analysis of the DNA binding properties of three metallopeptides to the Drew–Dickerson dodecamer DNA: Co II ‐Gly 1 ‐Gly 2 ‐His, Ni II ‐Gly 1 ‐Gly 2 ‐His and Cu II ‐Gly 1 ‐Gly 2 ‐His. Fairly extensive MD simulations were run on each system until a stable binding mode for each ligand was sampled. Clustering analysis was used in an attempt to find representative structures for the most populated clusters sampled during the MD, and a QTAIM analysis was performed. Additionally, MM‐PBSA analysis was performed to obtain approximate binding energies for each complex. The results suggest that stable DNA–metallopeptide complexes are formed with each of the three ligands, and that the most stable interaction is with Co(GGH), then Ni(GGH), and finally Cu(GGH). Bond Critical Points (BCP) information between the minor groove of the DNA and the metallopeptides shows an increase in electronic density between Gly 1 , the His residues, and the oxygen atoms of the thymine nucleotide. Overall, we present a detailed theoretical study of the specific interactions involved and the binding properties of each complex formed.