Investigation on Human b Defensin using Molecular Dynamics Simulation Method
Molecular dynamics (MD) simulations are statistical mechanics-based tools for predicting microscopic and macroscopic properties/dynamics based on the details of molecule-molecule interactions. They have been widely applied in biomedical and engineering fields. The application of MD on human b defensins (hBDs) type 2 (hBD-2) and type 3 (hBD-3) is covered in this talk. hBDs belong to the human innate immune system and have microbicidal activities against bacteria, fungi, yeast, viruses, in addition to having chemotactic activities. In order to understand its functional mechanism in molecular detail, the binding structure of hBD-3 on model bacterial membrane was predicted using microsecond-long MD simulations and validated by solid-state NMR method. It was found that hBD-3 binds with bacterial membrane on the two loop regions. Free energy perturbation (FEP) calculation further clarified the contribution of each residue to the membrane binding, which showed that the tail region of hBD-3 drives the process. The results emphasized the importance of electrostatic interaction in hBD-3’s binding with bacterial membrane. Besides that, it was found that hBD-2 can bind on the receptor binding domain (RBD) of SARS-CoV-2 (Cov-2) at the same site as the receptor angiotensin-converting enzyme 2 (ACE2), thus blocking CoV-2 virus from attacking ACE2 expressing cells. The result supplies insight on the role human innate immune system plays in combating CoV-2 infection.
Interesting future research areas using simulation methods will also be proposed in this talk, including hBD-3 interactions with human chemokine receptors and explicit model bacterial membranes, and defensin binding with possible future coronaviruses.
Dr. Liqun Zhang currently works as a computational chemist in a biomedical drug discovery company in Boston. From 2015 to 2022, she was an Assistant Professor in Chemical Engineering Department of Tennessee Technological University (TTU). Prior to that, she worked as a postdoc in Case Western Reserve University (CWRU), initially briefly at Chemical Engineering department, then at Physiology and Biophysics department of CWRU Medical School. She was awarded Ruth Kirschstein NRSA Postdoc Fellowship from NIH in 2012-2014. Dr. Zhang obtained both her Bachelor and Master’s degrees in Chemical Engineering from Zhejiang University of China, and her PhD in Chemical Engineering from University of Rhode Island (URI). Her lab in TTU mainly focused on studying the structure and dynamics of human b defensin (a family of small antimicrobial peptides) interacting with bacterial membranes, chemokine receptors and covid-19 virus. Her projects had been supported with 2 NSF, 1 DOD, 1 BWF medical foundation and 1 Covid-19 Patient Grants, in addition to 6 years of Faculty Research Grants from TTU. She had supervised 2 PhD, 5 Master and many undergraduate students, and worked as a session chair/co-chair in AIChE meetings for multiple years. Dr. Zhang has published over 38 peer-reviewed journal papers in chemical engineering and biophysics fields. Her research interests involve using molecular dynamic simulations to study the structure, dynamics/properties, and functional relationships of complex systems, including proteins such as hBDs, chemokine receptors, and model cell membranes.