Computational Analysis of <i>CC2D1A</i> Missense Mutations: Insight into Protein Structure and Interaction Dynamics
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide CC2D1A is implicated in a range of conditions, including autism spectrum disorder, intellectual disability, seizures, autosomal recessive nonsyndromic intellectual disability, heterotaxy, and ciliary dysfunction. In order to understand the molecular mechanisms underlying these conditions, we focused on the structural and dynamic activity consequences of mutations within this gene. In this study, whole exome sequencing identified the c.1552G > A (GLU518LYS) missense mutation in the CC2D1A in an 18-year-old male, linking it to intellectual disability and autism. In addition to the GLU518LYS mutation, we conducted a comprehensive analysis of other predefined missense mutations (i.e., PRO192LEU, GLN506ARG, PRO532LEU, GLY781VAL, and GLY781GLU) found within the CC2D1A . Utilizing all-atom molecular dynamics (MD) simulations and neighborhood interaction analyses, we delve into the impact of these mutations on protein structure and function at an atomic level, aiming to shed light on their contribution to the pathogenesis of related diseases. The results suggest that GLU518LYS, GLY781VAL, and GLY781GLU mutations did not significantly alter overall global protein structure compared to the wild type, while PRO192LEU, GLN506ARG, and PRO532LEU exhibited slightly higher protein root-mean-square deviation (RMSD) values, which may indicate potential impacts on whole protein stability. Moreover, neighborhood interaction analysis indicated that ASP85 emerges as a unique interaction partner specifically associated with the GLU518LYS mutation, whereas LYS75, which interacts with the ASP85 in the mutated form, is absent in the wild type. This alteration signifies a crucial reconfiguration in the local interaction network at the site of the mutation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".