Author ORCID Identifier


Defense Date


Document Type


Degree Name

Doctor of Philosophy


Pharmaceutical Sciences

First Advisor

Youzhong Guo

Second Advisor

Glen E. Kellogg


Functional insights into macromolecules lie in the arrangement of their molecular structures. Investigating the atomic framework of a biomolecule could unwind its biochemical mechanism, providing aid to many relevant biological questions, thus facilitating drug discovery processes. Two approaches have been used to gain knowledge at the atomic level of a protein function: experimental and computational methodologies.

From an experimental perspective, membrane proteins (MPs) were investigated. Such proteins represent ~20% of the human proteome, and ~60% of them are drug targets since they are exposed to the surface of cells and are responsible for a wide range of fundamental functions like cellular signaling, nutrient uptake, and motility, to name a few. However, despite the acknowledged importance and the tremendous effort toward their study, their extraction in the active, folded form remains challenging. Successful membrane protein folding, and the resulting activity, also involve the presence of the lipid environment. In our lab, the development of a detergent-free native cell membrane nanoparticles system (NCMN) allows the co-extraction and stabilization of membrane proteins in their near-to-native conformation. The proposed system can be combined with Single-Particle Cryogenic Electron Microscopy (Cryo-EM) analysis for high-resolution structures applicable to prokaryotic and eukaryotic membrane proteins. For instance, we have been working on two different classes of MPs: the bacteria mechanosensitive channels (Ms) and one of the gap junction channels (GJC), the human connexin 26.

Computationally, we proposed a new paradigm for structure model building and refinement exploiting 3D hydropathic interaction maps to achieve a synthetic native-like protein structure model. To reach this goal, we have been working in characterizing residue environments by assembling a database of residue type and backbone angle-dependent 3D maps. Such 3D maps fully describe the sets of preferred conformations and interaction environments surrounding each residue.


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Available for download on Tuesday, August 11, 2026