Atomic Resolution Insight into Sac7d Protein Binding to DNA and Associated Global Changes by Molecular Dynamics Simulations. Issue 18 (26th March 2019)

• Record Type: Journal Article
• Authors: Zacharias, Martin
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 18(2019)
• Page Start: 5967
• Page End: 5972
• Publication Date: 2019-03-26
• Subjects: DNA intercalation -- ligand–receptor binding -- molecular dynamics simulations -- protein–DNA interaction -- protein–DNA recognition; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201900935
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Sac7d is a small, thermostable protein that induces large helical deformations in DNA upon association. Starting from multiple initial placements of the unbound Sac7d structure relative to a B‐DNA oligonucleotide, molecular dynamics (MD) simulations were employed to directly follow several successful binding events at atomic resolution that resulted in structures in close agreement with the native complex geometry. The final native complex formed rapidly within tenths of nanoseconds and included simultaneous large‐scale kinking, groove opening, twisting, and intercalation in the target DNA. The simulations indicate that the complex formation process involves initial non‐native contacts that helped in reaching the final bound state, with residues intercalated at the center of the kinked DNA. It was also possible to identify several long‐lived trapped intermediate states of the binding process and to follow sliding processes of Sac7d along the DNA minor groove. Abstract : Molecular dynamics simulations were used to follow complex formation between the Sac7d protein and DNA. Several simulations are in close agreement with the native complex structure, including intercalation‐induced large‐scale DNA conformational changes. This study provides atomic‐level insight into the recognition process, role of water molecules, intermediate states, identification of trapped binding states, and Sac7d sliding along DNA.