School of Physics Soft Condensed Matter & Physics of Living Systems Seminar: Prof. Jana Shen, University of Maryland School of Pharmacy.

Protein and chitosan are two types of biopolymers abundant in nature. Proteins are the “workhorse” molecules of life and their dynamical behavior governs human physiological functions and underlies many diseases. Chitosan, a polysaccharide produced from shellfish, can be used to make smart hydrogels that find a wide range of applications in medicine, pharmacy, and bioelectronics. In this talk, I will introduce a computer simulation tool called continuous constant pH molecular dynamics (CpHMD) and discuss how it can be used to advance the understanding of the electrostatic mechanisms and dynamical behavior of proteins and chitosan-based materials. In the first two examples, CpHMD was used to reveal nucleophilic hotspots [1] and conformational landscape of protein kinases [2], which are cellular signaling molecules involved in cancer and many other diseases.

These studies led to a new strategy for targeted covalent inhibitor design and suggested a paradigm shift in our understanding of conformational plasticity of kinases, which presents a challenge but also opportunity in kinase drug discovery. In the later examples, CpHMD was used to explore pHresponsive self-assembly [3] and switchable crosslinking mechanisms for programming hydrogel materials [4]. Our work demonstrated a pKa gradient for a dynamical polysaccharide system and how it allows a persistent but erasable gradient in the structural and mechanical properties of the formed hydrogel