A5037737691- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Machine Learning in Bioinformatics
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Pharmacological Receptor Mechanisms and Effects
- Escherichia coli research studies
- Cholesterol and Lipid Metabolism
- Computational Drug Discovery Methods
Vanderbilt University
2019-2023
Icahn School of Medicine at Mount Sinai
2015
As sequencing methodologies continue to advance, the availability of protein sequences far outpaces ability structure determination. Homology modeling is used bridge this gap but relies on high-identity templates for accurate model building. G-protein coupled receptors (GPCRs) represent a significant target class pharmaceutical therapies in which homology could fill knowledge structure-based drug design. To date, only about 17% druggable GPCRs have had their structures characterized at...
With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators opioid receptors. In past two years, first chemotypes positive or silent (PAMs SAMs, respectively) μ- and δ-opioid receptor types have been reported in literature. During a structure-guided lead optimization campaign μ-PAMs BMS-986121 BMS-986122 as starting compounds, we discovered new chemotype that was confirmed display μ-PAM μ-SAM activity depending on...
Lipid molecules such as cholesterol interact with the surface of integral membrane proteins (IMP) in a mode different from drug-like protein binding pocket. These differences are due to lipid molecule’s shape, membrane’s hydrophobic environment, and lipid’s orientation membrane. We can use recent increase experimental structures complex understand protein-cholesterol interactions. developed RosettaCholesterol protocol consisting (1) prediction phase using an energy grid sample score...
Abstract G-protein coupled receptors (GPCRs) represent a significant target class for pharmaceutical therapies. However, to date, only about 10% of druggable GPCRs have had their structures characterized at atomic resolution. Further, because the flexibility GPCRs, alternative conformations remain be modeled, even after an experimental structure is available. Thus, computational modeling crucial component understanding biological function and aid development new therapeutics. Previous...
ABSTRACT Cholesterol (CLR) is an integral component of mammalian membranes. It has been shown to modulate membrane dynamics and alter protein (IMP) function. However, understanding the molecular mechanisms these processes complicated by limited conflicting structural data: Specifically, in co-crystal structures CLR-IMP complexes it difficult distinguish specific biologically relevant interactions from a nonspecific association captured crystallization process. The only widely recognized...