A. Berçin Barlas
@aysebercinb.bsky.social
Postdoctoral Researcher @Izmir Biomedicine and Genome Center - Computational Structural Biology Lab.
This is the first systematic dynamic analysis of shape readout in DNMT3 enzymes, showing how small molecular changes can lead to big functional differences --and laying groundwork for engineering paralog-specific protein-DNA interactions.
A long journey, but rewarding! 🌱
A long journey, but rewarding! 🌱
August 22, 2025 at 10:53 AM
This is the first systematic dynamic analysis of shape readout in DNMT3 enzymes, showing how small molecular changes can lead to big functional differences --and laying groundwork for engineering paralog-specific protein-DNA interactions.
A long journey, but rewarding! 🌱
A long journey, but rewarding! 🌱
Altogether,
✅ DNMT3A uses a rigid, precise strategy, while DNMT3B is more flexible and adaptable.
In other words,
✅ DNMT3A is a specialist with a pre-organized catalytic loop, while DNMT3B is a generalist with a flexible catalytic loop supporting its adaptability.
✅ DNMT3A uses a rigid, precise strategy, while DNMT3B is more flexible and adaptable.
In other words,
✅ DNMT3A is a specialist with a pre-organized catalytic loop, while DNMT3B is a generalist with a flexible catalytic loop supporting its adaptability.
August 22, 2025 at 10:52 AM
Altogether,
✅ DNMT3A uses a rigid, precise strategy, while DNMT3B is more flexible and adaptable.
In other words,
✅ DNMT3A is a specialist with a pre-organized catalytic loop, while DNMT3B is a generalist with a flexible catalytic loop supporting its adaptability.
✅ DNMT3A uses a rigid, precise strategy, while DNMT3B is more flexible and adaptable.
In other words,
✅ DNMT3A is a specialist with a pre-organized catalytic loop, while DNMT3B is a generalist with a flexible catalytic loop supporting its adaptability.
We found that subtle amino acid substitutions reshape DNA recognition:
⚡ DNMT3A uses Arg836 → rigid hydrogen bonding + electrostatic anchoring, favors pyrimidines (C/T).
🤸♀️ DNMT3B replaces Arg836 with Lys777 and introduces Asn779 → flexible and cooperative readout with broader substrate tolerance.
⚡ DNMT3A uses Arg836 → rigid hydrogen bonding + electrostatic anchoring, favors pyrimidines (C/T).
🤸♀️ DNMT3B replaces Arg836 with Lys777 and introduces Asn779 → flexible and cooperative readout with broader substrate tolerance.
August 22, 2025 at 10:50 AM
We found that subtle amino acid substitutions reshape DNA recognition:
⚡ DNMT3A uses Arg836 → rigid hydrogen bonding + electrostatic anchoring, favors pyrimidines (C/T).
🤸♀️ DNMT3B replaces Arg836 with Lys777 and introduces Asn779 → flexible and cooperative readout with broader substrate tolerance.
⚡ DNMT3A uses Arg836 → rigid hydrogen bonding + electrostatic anchoring, favors pyrimidines (C/T).
🤸♀️ DNMT3B replaces Arg836 with Lys777 and introduces Asn779 → flexible and cooperative readout with broader substrate tolerance.
To answer this, we ran 16 μs MD sims and built a new framework: Comparative Dynamics Analysis (CDA).
CDA integrates two complementary perspectives:
➡️ Base readout: base-specific hydrogen bonds at major groove
➡️ Shape readout: DNA deformation, electrostatics, and hydrophobic contacts at minor groove
CDA integrates two complementary perspectives:
➡️ Base readout: base-specific hydrogen bonds at major groove
➡️ Shape readout: DNA deformation, electrostatics, and hydrophobic contacts at minor groove
August 22, 2025 at 10:49 AM
To answer this, we ran 16 μs MD sims and built a new framework: Comparative Dynamics Analysis (CDA).
CDA integrates two complementary perspectives:
➡️ Base readout: base-specific hydrogen bonds at major groove
➡️ Shape readout: DNA deformation, electrostatics, and hydrophobic contacts at minor groove
CDA integrates two complementary perspectives:
➡️ Base readout: base-specific hydrogen bonds at major groove
➡️ Shape readout: DNA deformation, electrostatics, and hydrophobic contacts at minor groove