Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS
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arXiv
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| Natura: | Preprint |
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2024
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| author | Vakili, Mohammad Ghazi Gorgulla, Christoph Nigam, AkshatKumar Bezrukov, Dmitry Varoli, Daniel Aliper, Alex Polykovsky, Daniil Das, Krishna M. Padmanabha Snider, Jamie Lyakisheva, Anna Mansob, Ardalan Hosseini Yao, Zhong Bitar, Lela Radchenko, Eugene Ding, Xiao Liu, Jinxin Meng, Fanye Ren, Feng Cao, Yudong Stagljar, Igor Aspuru-Guzik, Alán Zhavoronkov, Alex |
| author_facet | Vakili, Mohammad Ghazi Gorgulla, Christoph Nigam, AkshatKumar Bezrukov, Dmitry Varoli, Daniel Aliper, Alex Polykovsky, Daniil Das, Krishna M. Padmanabha Snider, Jamie Lyakisheva, Anna Mansob, Ardalan Hosseini Yao, Zhong Bitar, Lela Radchenko, Eugene Ding, Xiao Liu, Jinxin Meng, Fanye Ren, Feng Cao, Yudong Stagljar, Igor Aspuru-Guzik, Alán Zhavoronkov, Alex |
| contents | The discovery of small molecules with therapeutic potential is a long-standing challenge in chemistry and biology. Researchers have increasingly leveraged novel computational techniques to streamline the drug development process to increase hit rates and reduce the costs associated with bringing a drug to market. To this end, we introduce a quantum-classical generative model that seamlessly integrates the computational power of quantum algorithms trained on a 16-qubit IBM quantum computer with the established reliability of classical methods for designing small molecules. Our hybrid generative model was applied to designing new KRAS inhibitors, a crucial target in cancer therapy. We synthesized 15 promising molecules during our investigation and subjected them to experimental testing to assess their ability to engage with the target. Notably, among these candidates, two molecules, ISM061-018-2 and ISM061-22, each featuring unique scaffolds, stood out by demonstrating effective engagement with KRAS. ISM061-018-2 was identified as a broad-spectrum KRAS inhibitor, exhibiting a binding affinity to KRAS-G12D at $1.4 μM$. Concurrently, ISM061-22 exhibited specific mutant selectivity, displaying heightened activity against KRAS G12R and Q61H mutants. To our knowledge, this work shows for the first time the use of a quantum-generative model to yield experimentally confirmed biological hits, showcasing the practical potential of quantum-assisted drug discovery to produce viable therapeutics. Moreover, our findings reveal that the efficacy of distribution learning correlates with the number of qubits utilized, underlining the scalability potential of quantum computing resources. Overall, we anticipate our results to be a stepping stone towards developing more advanced quantum generative models in drug discovery. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2402_08210 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS Vakili, Mohammad Ghazi Gorgulla, Christoph Nigam, AkshatKumar Bezrukov, Dmitry Varoli, Daniel Aliper, Alex Polykovsky, Daniil Das, Krishna M. Padmanabha Snider, Jamie Lyakisheva, Anna Mansob, Ardalan Hosseini Yao, Zhong Bitar, Lela Radchenko, Eugene Ding, Xiao Liu, Jinxin Meng, Fanye Ren, Feng Cao, Yudong Stagljar, Igor Aspuru-Guzik, Alán Zhavoronkov, Alex Quantum Physics Computational Engineering, Finance, and Science Computer Science and Game Theory Machine Learning The discovery of small molecules with therapeutic potential is a long-standing challenge in chemistry and biology. Researchers have increasingly leveraged novel computational techniques to streamline the drug development process to increase hit rates and reduce the costs associated with bringing a drug to market. To this end, we introduce a quantum-classical generative model that seamlessly integrates the computational power of quantum algorithms trained on a 16-qubit IBM quantum computer with the established reliability of classical methods for designing small molecules. Our hybrid generative model was applied to designing new KRAS inhibitors, a crucial target in cancer therapy. We synthesized 15 promising molecules during our investigation and subjected them to experimental testing to assess their ability to engage with the target. Notably, among these candidates, two molecules, ISM061-018-2 and ISM061-22, each featuring unique scaffolds, stood out by demonstrating effective engagement with KRAS. ISM061-018-2 was identified as a broad-spectrum KRAS inhibitor, exhibiting a binding affinity to KRAS-G12D at $1.4 μM$. Concurrently, ISM061-22 exhibited specific mutant selectivity, displaying heightened activity against KRAS G12R and Q61H mutants. To our knowledge, this work shows for the first time the use of a quantum-generative model to yield experimentally confirmed biological hits, showcasing the practical potential of quantum-assisted drug discovery to produce viable therapeutics. Moreover, our findings reveal that the efficacy of distribution learning correlates with the number of qubits utilized, underlining the scalability potential of quantum computing resources. Overall, we anticipate our results to be a stepping stone towards developing more advanced quantum generative models in drug discovery. |
| title | Quantum Computing-Enhanced Algorithm Unveils Novel Inhibitors for KRAS |
| topic | Quantum Physics Computational Engineering, Finance, and Science Computer Science and Game Theory Machine Learning |
| url | https://arxiv.org/abs/2402.08210 |