Hot Links >>


Conference >>


For Participants >>


Media Partners >>



Jung-Hsin Lin
Prof. Jung-Hsin Lin
Research Center for Applied Sciences, Academia Sinica, Chinese Taipei
Harnessing Structures and Dynamics of Biomolecules for Computational Drug Design

Biomolecules are in constantmotion under physiological condition. The apparent limitation of docking to a static protein structure has received increasing attention, and some proper incorporation of protein flexibility has been called to include the effects of induce-fit and the conformation selection of ligands.In the past decade we continue to extend the “relaxed complex” scheme, which incorporated the protein dynamics by rapid docking to the conformation ensemble generated by molecular dynamics simulations. To make more efficient use of computing resources, we proposed a novel global optimization algorithm that could work at the high dimensionality that is relevant to most protein-ligand interaction problems. With the help of the robust regression analysis, we have developed new scoring functions in combination with quantum chemical charge models, which can be used not only to more accurately predict the binding poses of ligands on the protein pockets, but also the binding affinities of ligands to their target proteins. Encouraged by the generally applicability of the new scoring functions, we constructed a web server that allows docking the small molecule again the protein structures in the Protein Databank to help predict its possible targets. Besides, we have proposed an iterative docking scheme to automatically predict multiple binding sites or contiguous conformation of substrates along the pathways or channels inside the proteins. 

As an example, I will talk about molecular dynamics simulations of several isoforms of histone deacetylases (HDACs). Comparisons with different ways (Lennard-Jones 12-6, 12-6-4, and QM/MM) of treating the interactions of the Zn2+ ion with its surrounding residues will be discussed, with a special emphasis on the changes in the Zn2+ coordination numbers. 

1. Jung-Hsin Lin*.Structure- and dynamics-based computational design of anticancer drugs. Biopolymers 105: 2-9 (2016) 

2. Nanlan Huang and Jung-Hsin Lin*. Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation. Nucleic Acids Res. 43: 6772-6786 (2015) 

3. Jui-Chih Wang and Jung-Hsin Lin*. Scoring function for fragment-based drug discovery. Chapter 9 of “Methods in Molecular Biology”, Anthony Klon (Editor), Springer Verlag (2015) ISBN 978-1-4939-2486-8 

4. Jhih-Bin Chen , Ting-RongChern , Tzu-Tang Wei , Ching-Chow Chen , Jung-Hsin Lin*, and Jim-Min Fang*.Design and synthesis of dual-action inhibitors targeting histone deacetylases and HMG-CoA reductase for cancer treatment. J. Med. Chem. 56: 3645-3655 (2013) 

5. Jui-Chih Wang and Jung-Hsin Lin*. Scoring functions for prediction of protein-ligand interactions. Curr. Pharm. Des. 19: 2174-2182 (2013) 

6. Jui-Chih Wang, Pei-Ying Chu, Chung-Ming Chen and Jung-Hsin Lin*.idTarget: a web server for identifying proteins targets of small chemical molecules with robust scoring functions and a divide-and-conquer docking approach.Nucleic Acids Res. 40: W393-W399 (2012) 

7. Jui-ChihWang,Jung-Hsin Lin*,Chung-Ming Chen, Alex L. Perryman, Arthur J. Olson.Robust scoring functions for protein-ligand interactions with quantum chemical charge models.J. Chem. Inf. Model. 51: 2528-2537 (2011)


Dr. Jung-Hsin Lin was born in Taipei in 1968.  He received his B. Sc. and M. Sc. in Physics at Department of Physics, National Taiwan University (NTU), and Ph.D. (Dr. rer. nat.) in Biophysics at Institut für Festkörperforschung (Institute of Condensed Matter Research), Forschungszentrum Jülich (Research Center Jülich), Germany, under the supervision of Dr. Artur Baumgaertner.


After his postdoctoral research at John von Neuman Institute for Computing (NIC) at Forschungszentrum Jülich, he worked as Bioinformatics Specialist at Howard Hughes Medical Institute at University of California, San Diego (UCSD), U.S.A., under the supervision of Professor J. Andrew McCammon. During this period of time, he and his colleagues in UCSD proposed the relaxed complex scheme [J. Am. Chem. Soc. 124 5632-5633 (2002)] to accommodate thedynamics of biomolecules in molecular docking and structure-based computational drug design. This method was the first that successfully reproduced the “SAR by NMR” (a paradigm in fragment-based drug discovery) experimental results. After he returned to Taiwan, he and his colleagues in NTU proposed novel efficient global optimization algorithm for the molecular docking problem, and his lab proposed generally-applicable robust scoring functions for protein-ligand interactions.  He is a Research Fellow of Research Center for Applied Sciences (RCAS), Academia Sinica, and he has joint appointments with Institute of Biomedical Sciences (IBMS), Academia Sinica, School of Pharmacy, NTU, and College of Engineering, Chang Gung University. His major research topics are on the developments and applications of computational methodologies for design and discovery of new drugs, and for unraveling the molecular mechanisms of biological systems based on fundamental physical chemical principles, with the help of molecular modeling and simulations.


Prof. Lin is a member of American Chemical Society, U.S. Biophysical Society, and Taiwan Biophysical Society.  He frequently gave seminars and sometimes plenary lectures in international conferences.  He serves as reviewers for more than 30 scientific journals, and he is currently serving in the Editorial Board of Advances in Physics X.  He is the Chief Executive Officer of the Thematic Center for Biomedical Applications of RCAS since January, 2015.  


Home | About Engii | Contact Us
Copyright © 2007 - 2017 Engineering Information Institute. All rights reserved.