Deep Dynamics Secures Dual JCIM Cover Features, Elucidating Mechanisms and Applications of Dynamics-Based Drug Discovery (DBDD)

Recently, Zheng Zheng's team from Divamics Inc. has consecutively published two cover articles in top journals, providing an in-depth explanation of the technical mechanisms and real-world application scenarios of Dynamics-based Drug Discovery (DBDD).

This cover article of the October 2022 issue of the Journal of Chemical Information and Modeling (JCIM) provides an in-depth explanation of the collaborative project results among Divamics' technical team, Wuhan University of Technology, and QuantumBio Inc., a U.S.-based computer-aided drug design software company. The paper was co-authored by Wenlang Liu, Zhenhao Liu, Hao Liu, Lance M. Westerhoff, and Zheng Zheng.

Divamics Technical Team and QuantumBio Inc. have been continuously developing the Movable Type (MT) molecular binding free energy algorithm through long-term collaboration, incorporating various sampling methods such as induced-fit molecular docking, long-timescale molecular dynamics simulations, and Monte Carlo combined with multi-trajectory molecular dynamics simulations into the computational workflow for target-drug-like compound binding free energy.

Fig./J. Chem. Inf. Model. 2022, October Issue Cover

This platform provides diversified DBDD solutions for new drug researchers when targeting sites with different conformational characteristics, enabling the selection of the optimal balance between computational accuracy and speed across various new drug development scenarios. Particularly, when the MT algorithm platform is combined with multi-scale molecular dynamics simulation sampling methods, it extends the universality of free energy calculations to a broader range of target-ligand compound systems.

The MovableType algorithm software suite is currently widely used by pharmaceutical companies worldwide. "Since we launched MovableType two years ago, we have explored numerous cases with our clients, and this method has brought significant value to them," said Dr. Westerhoff, President and General Manager of QuantumBio.

The cover article of the July 2022 issue of JCIM elaborated on the collaborative project achievements of Divamics' technical team with Wuhan University of Technology and the Chinese Academy of Sciences Precision Measurement Science and Innovation. This work utilized meta-dynamics methods to analyze the flexibility mechanisms of the c-Met target protein, which plays a crucial role in pathways such as RAS, PI3K, and STAT.

The paper was co-authored by Tao Jiang, Zhenhao Liu, Wenlang Liu, Jiawen Chen, Zheng Zheng, and Mojie Duan.Exploring the DFG domain transition of c-Met kinase reveals two conversion pathways, one of which, Pathway II, has not been previously reported in earlier studies.The intermediate states existing in the newly discovered pathway can serve as special receptor conformations. By utilizing computer-aided drug design methods, it is possible to develop drugs with strong selectivity for c-Met kinase. In addition,The combination of traditional molecular dynamics with metadynamics enhanced sampling methods can also be applied to other kinases to explore hidden transition mechanisms.

Fig./J. Chem. Inf. Model. 2022, July Issue Cover

Dr. Zheng Zheng, Founder of Divamics Inc. Ph.D. in Chemistry from the University of Florida, Bachelor of Pharmacy from Peking University; studied under Professor Kenneth Merz, a world-leading expert in computational chemistry; expert in computer-aided drug design and machine learning, inventor of core algorithms for projects; Senior Scientist at QuantumBio drug design software company in the U.S.; Professor and Ph.D. supervisor at Wuhan University of Technology, selected for Hubei Province's "Hundred Talents Plan," recipient of China's Industry-University-Research Cooperation Innovation Award and Suzhou Industrial Park Science and Technology Leadership Talent title; has published over 40 academic papers in top international journals, authored one academic book, led and participated in two NIH projects in the U.S. and one National Natural Science Foundation of China project; led the commercial transformation of multiple international patents; serves as an editorial board member for the top international journal in cheminformatics, J. Chem. Inf. Model.

 Photo/Dr. Zheng Zheng, Founder of Divamics Inc.

Liu Wenlang, Jiang Tao, and Liu Zhenhao are co-authors of two top journal cover articles and serve as technical engineers at Divamics Inc.

Fig./Group photo of the authors of the top journal cover article, with Jiang Tao on the left, Liu Zhenhao in the middle, and Liu Wenlang on the right.

Divamics is a cross-disciplinary technology-driven biopharmaceutical company that leverages artificial intelligence, quantum mechanics, and molecular simulation algorithms as its core technologies to empower new drug discovery through computational simulation.

In 2021, Divamics Inc. established an internationally leading next-generation artificial intelligence (AI) drug discovery platform by integrating its self-innovated AI technology with a core algorithm for high-precision molecular dynamics simulations. This AI platform focuses on achieving high-precision structural analysis and simulating physiological dynamic processes for unresolved and highly flexible targets, enabling the discovery of new drugs for challenging targets. Since its inception, the company has been recognized as a leading technological enterprise in the Suzhou Industrial Park. Currently, Divamics Inc. is collaborating with several domestic and international biopharmaceutical companies to advance multiple drug development pipelines and has achieved breakthrough results in several directions targeting difficult-to-drug targets.

*References

[1]J. Chem. Inf. Model. 2022, 62, 5645−5665

[2]J. Chem. Inf. Model. 2022, 62, 3651−3663