Advisory Board

Professor Chenglong Li

The Scientist Live article Spice-based compound to fight against cancer said

Seeking to improve on nature, scientists used a spice-based compound as a starting point and developed synthetic molecules that, in lab settings, are able to kill cancer cells and stop the cells from spreading.
 
The researchers are combining organic chemistry, computer-aided design and molecular biology techniques in developing and testing pharmaceutical compounds that can fight breast and prostate cancer cells. The synthetic molecules are derived from curcumin, a naturally occurring compound found in the spice turmeric.
 
Centuries of anecdotal evidence and recent scientific research suggest curcumin has multiple disease-fighting features, including anti-tumor properties. However, when eaten, curcumin is not absorbed well by the body. Instead, most ingested curcumin in food or supplement form remains in the gastrointestinal system and is eliminated before it is able to enter the bloodstream or tissues.
 
“Most of the interaction between our compound and the overactive protein comes from what are called hot spots on the protein’s surface,” said Chenglong Li, assistant professor of medicinal chemistry and pharmacognosy at Ohio State and an expert in computational chemistry. “For each spot, we can design small chemical fragments and link them together to make a molecule. This is what computer-aided design and modeling can do.”

Chenglong Li, Ph.D. is Assistant Professor, Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University.
 
Chenglong’s long-standing scientific interest is to understand the structure and dynamics of matter at the atomic/molecular level (“the jigglings and wigglings of atoms” from the wonderful Feynman Lectures on Physics), and their relationship to the functions and properties of our physical and biological macro-world (the spatial-temporal collective behavior).
 
His research domains span from X-ray macromolecular crystallography, molecular docking, molecular dynamics, and quantum chemistry to statistical mechanics and non-equilibrium and equilibrium thermodynamics. Since the underlying complexity makes most of the research problems analytically intractable, computational approaches have to be adopted (the so-called third science of computation/simulation after theory and experiment).
 
Specifically, he starts with the study of molecular recognition because molecular recognition between biomolecules like proteins, DNAs, RNAs, and small ligands is of central importance in biological and pharmacological processes like signal transduction, DNA transcription, enzymatic reaction, and drug action. Whether two molecules bind to each other or not and how strong that binding is dependent on the binding free energy differences. Therefore, predicting absolute and relative binding free energies of molecular associations is of great scientific and practical value. In fact, free energy calculation remains one of the most challenging issues in current computational sciences, even though great progress has been made and creative approaches have been developed over the past few decades.
 
His projects include:
 
1) Structure-based/computer-aided drug design (SBDD/CADD)

  • Anti-cancer drug design targeting BCL-2/BCL-xL, DNA methyltransferase (DNMT), thymidine kinase (TK), STAT3, and tubulin.
  • Anti-diabetic (type 2) and anti-metabolic syndrome (MS) drug design targeting 11Β-HSD type 1.

2) Molecular docking and free energy simulation

  • Molecular docking. Both sampling and scoring need to be improved.
  • Free energy simulation. Both better “end-point” evaluation and fast and efficient “phase-mapping” are to be explored.

3) X-ray macromolecular crystallography

  • The determination of 3D structures of biologically important proteins/DNAs/RNAs or their complexes (molecular machines).
  • The development of crystallographic computing methods for both phase solution (reciprocal space) and structure refinement (real space).

Chenglong coauthored Structural Analysis of Siah1-Siah-interacting Protein Interactions and Insights into the Assembly of an E3 Ligase Multiprotein Complex, The Serine-rich Domain from Crk-associated Substrate (p130cas) is a Four-helix Bundle, Crystal Structure of Avian Aminoimidazole-4-carboxamide Ribonucleotide Transformylase in Complex with a Novel Non-folate Inhibitor Identified by Virtual Ligand Screening, Structurally Distinct Recognition Motifs in Lymphotoxin-Β Receptor and CD40 for Tumor Necrosis Factor Receptor-associated Factor (TRAF)-mediated Signaling, Structural Basis for Substrate Specificity of Escherichia coli Purine Nucleoside Phosphorylase, and Conformational restrictions in the active site of unliganded human caspase-3.
 
He also coauthored Analysis of efficacy of chiral adrenergic agonists, Structure-based Design, Synthesis, Evaluation, and Crystal Structures of Transition State Analogue Inhibitors of Inosine Monophosphate Cyclohydrolase, Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis, Virtual Screening of Human AICAR Transformylase against the NCI Diversity set Using AutoDock to Identify Novel Non-folate Inhibitors, Downstream Regulator TANK binds to the CD40 Recognition Site on TRAF3, and X-ray Crystal Structure of Aminoimidazole Ribonucleotide Synthetase (PurM) from the Escherichia coli Purine Biosynthetic Pathway at 2.5 Å Resolution.
 
Chenglong earned his B.Sc. in Chemistry at Peking (Beijing) University, China in 1985, his M.Sc. in Physical Chemistry at Peking (Beijing) University, China in 1988, and his Ph.D. in Biophysics at Cornell University in 2000. He is a member of The American Chemical Society, The American Crystallographic Association, and The American Association for Cancer Research.