The role of residue 50 and hydration water molecules in homeodomain DNA recognition.
We conducted molecular dynamics simulations on several wild-type and mutant homeodomain-DNA complexes to investigate the role of residue 50 in homeodomain-DNA interaction and the behavior of interfacial hydration water. Our results suggest that this residue interacts more favorably with its consensus sequence and thus plays a considerable role in DNA recognition. However, residue 50 was not responsible for DNA recognition alone. Other residues in the vicinity could interact with residue 50 in cooperation upon DNA binding. We also found the lifetime for some water in the protein-DNA interface can be as high as nanoseconds and that a few well-conserved sites for water-mediated hydrogen bonds from protein to DNA are occupied by high-mobility hydrating waters.
Duan
Jianxin
J
Karolinska Institute, Department of Biosciences at Novum, 141 57 Huddinge, Sweden.
Nilsson
Lennart
L
D001483:Base Sequence; D003198:Computer Simulation; D016384:Consensus Sequence; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D018398:Homeodomain Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D046911:Macromolecular Substances; D014867:Water; D004247:DNA