MindNexQua: De Novo İlaç Tasarımı ve İn Siliko Moleküler Docking Yönetimi için Otonom Üretken Yapay Zeka Sistemi

Öz

İlaç geliştirme süreçleri; uzun zaman gereksinimleri, yüksek maliyetler ve klinik denemelerde %15’in altında başarı oranları gibi önemli zorluklarla karşı karşıyadır. Bu maliyetli ve karmaşık süreçleri optimize etmek amacıyla, KOSTU Biyokimya Departmanı’ndan Soykan Ağar’ın araştırma grubu, MindNexQua (MNQ) adını verdikleri otonom bir yapay zekâ sistemi geliştirmiştir. Bu çalışma, pahalı lisanslı platformlara alternatif olarak erişilebilir, açık kaynaklı ve kendi kendine yeten bir sistem sunarak ilaç keşif sürecini güncellemeyi amaçlamaktadır. Sistem, hedef reseptör protein yapıları ve ilaç adayı ligandları başlangıç girdileri olarak kullanarak, in silico biyokimyasal kenetlenmeden, nihai görselleştirmeye kadar olan süreci otomatikleştiren bir iş akışı sunmaktadır. MNQ; yapısal türevlerin üretilmesi için RDKit’i, moleküler kenetlenme hesaplamaları için AutoDock Vina’yı ve sonuçların yorumlanması için Mistral 7B tabanlı büyük dil modellerini entegre etmektedir. Simülasyonların güvenilirliğini artırmak ve rastgele hataları en aza indirmek amacıyla, her bir ligand adayı için 20 bağımsız simülasyondan oluşan çoklu çalıştırma (multi-run) stratejisi uygulanmaktadır. Sürecin sonunda sistem, en düşük bağlanma enerjisine (ΔG) sahip en iyi 5 aday molekülü otomatik olarak seçmekte ve istatistiksel olarak doğrulamaktadır. Elde edilen bulgular, MNQ tarafından tasarlanan aday moleküllerin hedef proteinlerin aktif bölgelerine yüksek sterik uyum (-8,6 kcal/mol) gösterdiğini ve termodinamik olarak kararlı konformasyonlar sergilediğini ortaya koymaktadır. Sonuç olarak MNQ, de novo ilaç tasarımı ve in silico moleküler kenetlenme süreçlerinin koordinasyonu için sürdürülebilir, otonom ve entegre bir araştırma ekosistemi sunmaktadır.

Anahtar Kelimeler

• De Novo İlaç Tasarımı
• Yapay Zeka
• Moleküler Doklama
• Hibrit Kuantum Sinir Ağları

MindNexQua: An Autonomous Generative AI Framework for De Novo Drug Design and In Silico Molecular Docking Orchestration

Öz

Drug development processes face significant challenges, including lengthy time requirements, high costs, and success rates below 15% in clinical trials. To optimize these costly and complex processes, the KOSTU Biochemistry Department Soykan Agar’s research group has developed an autonomous artificial intelligence called MindNexQua (MNQ). This work aims to update the drug discovery pipeline by offering an accessible, open-source, and self-sufficient alternative to expensive licensed platforms. The system has a workflow that automates the process from in silico biochemical docking to final visualization, using target receptor protein structures and drug candidate ligands as initial input. MNQ integrates RDKit for the generation of structural derivatives, AutoDock Vina for molecular docking calculations, and Mistral 7B-based large language models for interpreting results. To improve the reliability of simulations and minimize random errors, a "multi-run" strategy consisting of 20 independent simulations is applied to each ligand candidate. At the end of this process, the system automatically selects and statistically validates the "Top-5" candidate molecule with the lowest binding energy (ΔG). The findings show that the candidate molecules designed by MindNexQua exhibit high steric fit (-8.6 kcal/mol) to the active site of target proteins and display thermodynamically stable conformations. Consequently, MNQ offers a sustainable, autonomous, and integrated research ecosystem for de novo drug design and in silico molecular docking orchestration.

Anahtar Kelimeler

• De Novo Drug Design
• AI
• Molecular Docking
• Hybrid Quantum Neural Networks

Kaynakça

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