Thermodynamic resilience of wild-type p53 DNA-binding domain and its disruption by the R273H hotspot mutation: Insights from REMD simulations

Q: What does this research mean for the field?

The R273H hotspot mutation significantly disrupts the thermodynamic resilience and structural stability of the p53 DNA-binding domain, challenging its conventional classification. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Ziqian Zhao; Gang Wang; Zhenyu Qian

doi:10.1039/d6cp00665e

January 1, 2026Physical Chemistry Chemical Physics

Thermodynamic resilience of wild-type p53 DNA-binding domain and its disruption by the R273H hotspot mutation: Insights from REMD simulations

View Full Paper

Ask AI

Bookmark

Share

Key Points

The research aims to understand how the R273H mutation affects the thermodynamic stability of the p53 DNA-binding domain.
Used replica-exchange molecular dynamics (REMD) simulations to analyze p53 DBD.
Compared wild-type p53 with the R273H mutant.
Evaluated thermodynamic stability through conformational sampling.
Wild-type p53 DBD exhibits greater thermodynamic resilience than the R273H variant.
The R273H mutation significantly disrupts the DNA-binding domain's stability.
Insights suggest that mutations compromising stability may interfere with tumor suppression functions.

Implication

Demonstrates the impact of the R273H mutation on p53 DNA-binding domain resilience, suggesting implications for tumor suppression.

Abstract

The p53 protein is a cornerstone of tumor suppression, yet its functional integrity is frequently compromised by mutations in the DNA-binding domain (DBD). While R273H is conventionally classified as a...

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Zhao et al. (2026) studied this question.

synapsesocial.com/papers/69cf5d885a333a821460b4a6 https://doi.org/10.1039/d6cp00665e

View Full Paper

Ask AI

Bookmark

Share

Thermodynamic resilience of wild-type p53 DNA-binding domain and its disruption by the R273H hotspot mutation: Insights from REMD simulations

Key Points

Implication

Abstract

Discussion

Cite This Study

Thermodynamic resilience of wild-type p53 DNA-binding domain and its disruption by the R273H hotspot mutation: Insights from REMD simulations

Key Points

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading