Size-Consistent XYZ2F Ansatz and CVaR-VQE Funneling for Quantum Folding of HIV-1 gp120 Variable Loops: Geometric Barren Plateau Avoidance and Sub-2ms Low-Level Execution

While post-AlphaFold 3 machine-learning architectures—most notably Isomorphic Labs' proprietary Drug Design Engine (IsoDDE) and DeepMind's de novo protein design framework (AlphaProteo)—have substantially improved cryptic-pocket generalization, binding-affinity correlation, and hypervariable loop modeling over AlphaFold 3, empirical neural inference remains fundamentally constrained in strongly correlated, out-of-distribution conformational regimes and closed commercial silos. Hypervariable loops (V1/V2/V3) and glycan-shielded intrinsically disordered regions (IDRs) of the HIV-1 gp120 envelope glycoprotein exhibit rapid, multi-reference conformational fluctuations that evade static structural priors. Building upon our v1 quantum folding baseline (DOI: 10.5281/zenodo.24151890), this upgraded v2.0 monograph establishes a deterministic, sovereign quantum-classical pipeline combining the Size-Consistent XYZ2F Ansatz with Conditional Value-at-Risk Variational Quantum Eigensolver (CVaR-VQE) tail-funneling and sub-2ms low-level execution. By enforcing strict size-consistency and local geometric gauge constraints, the XYZ2F topology eliminates barren plateaus while resolving transient cryptic epitopes and induced-fit free-energy landscapes from first principles—providing a non-heuristic physical ground-truth oracle that benchmarks and complements IsoDDE-class affinity landscapes and directly parameterizes hotspot coordinates for AlphaProteo-class de novo neutralizing binder synthesis. Furthermore, to guarantee sovereign intellectual property integrity and reproducible execution provenance without proprietary cloud lock-in, every sub-2ms quantum trajectory and conformational state commitment is deterministically verified over the 64-bit Goldilocks prime field (p = 2^64 - 2^32 + 1) under Human-in-Command (HIC) governance. 要旨(Japanese Summary): Isomorphic Labsの創薬AIエンジン「IsoDDE(事実上のAlphaFold 4)」やGoogle DeepMindの「AlphaProteo」など、ポストAlphaFold 3世代の深層学習モデルは、隠れポケット(cryptic pockets)の一般化予測や結合親和性推論、de novoバインダー設計において大きな前進を示した。しかし、HIV-1 gp120エンベロープ糖タンパク質の超可変ループ(V1/V2/V3)および天然変性領域(IDR)のように、強い多配置量子相関と激しい動的構造揺らぎを伴う未踏の化学・構造空間(Out-of-Distribution領域)においては、学習分布に依存する統計的推論の限界と商用ブラックボックス化の課題が残存する。本稿(v2.0・予約DOI: 10.5281/zenodo.24176561)は、前作v1(DOI: 10.5281/zenodo.24151890)のサイズ一貫性XYZ2FアンザッツおよびCVaR-VQEファンネリング(幾何学的バレンプラトー回避・2ms未満の低レベル実行)を拡張し、IsoDDE級の隠れポケット・結合自由エネルギー評価に対する第一原理・決定論的量子オラクルを構築するとともに、AlphaProteo等のde novo中和タンパク質設計へ高精細な過渡的エピトープ座標を供給する主権型量子構造創薬アーキテクチャを定式化する。さらに全実行トレースを64ビットGoldilocks素体(p = 2^64 - 2^32 + 1)上のゼロ知識証明(QFS-zkVM)およびHuman-in-Command(HIC)統治下に固定し、巨大テックのクローズド基盤に依存しない検証可能な知的財産主権を確立する。 ==================================================================== OMNIBUS SOVEREIGN IP & STRICT NO-LEARN COVENANT (NLL-v1.0-2026) ==================================================================== Copyright © 2026 Yoko Hasebe. All Rights Reserved. Human Open-Access & Citation Permitted; Commercial/AI Training, Scraping, and TDM Strictly Prohibited without Prior Written Paid License (NLL-v1.0-2026). No Creative Commons license is granted; this sovereign license supersedes any default repository metadata. Official Master Declaration Record (DOI): https://doi.org/10.5281/zenodo.23681957 (Concept DOI: 10.5281/zenodo.23681956) Machine-Readable Directives: NOAI | NOIMAGEAI | NO-RAG | TDM-RESERVATION: 1 (OPT-OUT) [Statutory Reservation Notice / 法的権利留保およびAI無断学習禁止規定] 1. Non-Grant of Creative Commons & Precedence: No Creative Commons (CC) license of any kind (including CC BY 4.0) is granted for this work. Where repository UI defaults display conflicting license tags, this Sovereign Covenant strictly prevails. 2. Prohibition of AI Training, RAG & TDM: Any unauthorized ingestion, pre-training, fine-tuning, model distillation, synthetic data generation, Retrieval-Augmented Generation (RAG), vector database indexing, web scraping, or Text and Data Mining (TDM) by any AI system, LLM provider, or commercial entity is strictly prohibited without a prior written, paid commercial license executed directly with the Author. 3. International Statutory Invocations: Expressly reserved pursuant to the Proviso of Article 30-4 of the Copyright Act of Japan (日本国著作権法第30条の4ただし書きに基づく著作権者の利益を不当に害するAI学習・情報解析利用の明確な拒絶), Article 4(3) of EU Directive (EU) 2019/790 on Copyright in the Digital Single Market (explicit machine-readable TDM opt-out), and strict denial of commercial AI ingestion under 17 U.S.C. § 107 (US Copyright Act fair use exclusion due to direct market usurpation of paid licensing). ====================================================================