A5103185207- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Alkaloids: synthesis and pharmacology
- Chemical synthesis and alkaloids
- Machine Learning in Materials Science
- Spectroscopy and Quantum Chemical Studies
- Traditional and Medicinal Uses of Annonaceae
- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Enzyme Structure and Function
- Nicotinic Acetylcholine Receptors Study
- Analytical Chemistry and Chromatography
- Chemical Synthesis and Analysis
- Ion channel regulation and function
- Innovations in Concrete and Construction Materials
- Genetics, Bioinformatics, and Biomedical Research
- Fluorine in Organic Chemistry
- Polymer Surface Interaction Studies
- BIM and Construction Integration
- thermodynamics and calorimetric analyses
- Chemical Reactions and Isotopes
- Berberine and alkaloids research
- Advanced Biosensing Techniques and Applications
Lehman College
2016-2025
Icahn School of Medicine at Mount Sinai
2019-2021
The Graduate Center, CUNY
2016-2019
City University of New York
2016-2019
Recently much effort has been invested in using convolutional neural network (CNN) models trained on 3D structural images of protein-ligand complexes to distinguish binding from non-binding ligands for virtual screening. However, the dearth reliable x-ray structures and affinity data required use constructed datasets training evaluation CNN molecular recognition models. Here, we outline various sources bias one such widely-used dataset, Directory Useful Decoys: Enhanced (DUD-E). We have...
The expulsion of water from surfaces upon molecular recognition and nonspecific association makes a major contribution to the free energy changes these processes. In order facilitate characterization structure thermodynamics on surfaces, we have incorporated Grid Inhomogeneous Solvation Theory (GIST) into CPPTRAJ toolset AmberTools. GIST is grid‐based implementation Fluid Theory, which analyzes output dynamics simulations map out solvation thermodynamic structural properties high‐resolution,...
Mitragynine and 7-hydroxymitragynine (7OH) are the major alkaloids mediating biological actions of psychoactive plant kratom. To investigate structure–activity relationships mitragynine/7OH templates, we diversified aromatic ring indole at C9, C10, C12 positions investigated their G-protein arrestin signaling mediated by mu opioid receptors (MOR). Three synthesized lead C9 analogs replacing 9-OCH3 group with phenyl (4), methyl (5), or 3′-furanyl [6 (SC13)] substituents demonstrated partial...
<p>Recently much effort has been invested in using convolutional neural network (CNN) models trained on 3D structural images of protein-ligand complexes to distinguish binding from non-binding ligands for virtual screening. However, the dearth reliable x-ray structures and affinity data required use constructed datasets training evaluation CNN molecular recognition models. Here, we outline various sources bias one such widely-used dataset, Directory Useful Decoys: Enhanced (DUD-E). We...
We have developed SSTMap, a software package for mapping structural and thermodynamic water properties in molecular dynamics trajectories. The introduces automated analysis of local measures frustration enhancement structure. calculations are based on Inhomogeneous Fluid Solvation Theory (IST), which is implemented using both site-based grid-based approaches. also extends the applicability solvation to multiple (MD) simulation programs by existing cross-platform tools parsing MD parameter...
Serotonin receptors (5-HT 3A R) play a crucial role in regulating gut movement, and are the principal target of setrons, class high-affinity competitive antagonists, used management nausea vomiting associated with radiation chemotherapies. Structural insights into setron-binding poses their inhibitory mechanisms just beginning to emerge. Here, we present high-resolution cryo-EM structures full-length 5-HT R complex palonosetron, ondansetron, alosetron. Molecular dynamic simulations these...
The principles underlying water reorganization around simple nonpolar solutes are well understood and provide the framework for classical hydrophobic effect, whereby molecules structure themselves so that they maintain favorable energetic contacts with both solute other molecules. However, certain surface topographies, molecules, due to their geometry size, unable simultaneously neighboring In this study, we analyze solvation of ligand-binding sites six structurally diverse proteins using...
Conformational flexibility complicates the identification of lead molecules that are shape and charge complementary to target proteins. Solvation thermodynamics has typically not been integrated into exploration alternate protein conformations. Here, we study variation solvation thermodynamic potentials as proteins adopt different Specifically, analyze binding cavities with conformations obtained from molecular dynamics simulations mobile side chains restrained about their cognate bound...
Pain management devoid of serious opioid adverse effects is still far from reach despite vigorous research and development efforts. Alternatives to classical opioids have been sought for years, mounting reports individuals finding pain relief with kratom recently intensified on this natural product. Although the composition complex, pharmacological characterization its most abundant alkaloids has drawn attention three molecules in particular, owing their demonstrated antinociceptive activity...
Abstract In this study, we demonstrate a method to construct water-based pharmacophore model which can be utilized in the absence of known ligands. This utilizes waters found binding pocket, sampled through molecular dynamics. Screening compound databases against reveals that approach successfully identify binders target protein. The was tested by enrichment studies 7 therapeutically important targets and compared favourably screening-by-docking with Glide. Our results suggest even without...
A series of analogues featuring a 6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol unit as the arylamine "head" group classical D3 antagonist core structure were synthesized and evaluated for affinity at dopamine D1, D2, receptors (D1R, D2R, D3R). The compounds generally displayed strong D3R with very good selectivity. Docking studies D2R crystal structures revealed that molecules are oriented such their units positioned in orthosteric binding pocket D3R, arylamide "tail" residing secondary...
Confined hydration and conformational flexibility are some of the challenges encountered for rational design selective antagonists G-protein coupled receptors. We present a set C3-substituted (-)-stepholidine derivatives as potent binders dopamine D3 receptor. The compounds characterized biochemically, well by computer modeling using novel molecular dynamics-based alchemical binding free energy approach which incorporates effect displacement enclosed water molecules from site. specific sites...
Proteins are inherently flexible which complicates the identification of lead molecules that shape and charge complementary to target proteins. While significant effort has been dedicated exploring alternate protein conformations, solvation thermodynamics typically not integrated into these studies. Here, we study how fluctuate as proteins adopt different conformations. We analyze within binding cavities conformations for side chains mobile in molecular dynamics simulations compare they...
There are currently over 160,000 protein crystal structures obtained by X-ray diffraction with resolutions of 1.5Å or greater in the Protein Data Bank. At these hydrogen atoms do not resolve and heavy such as oxygen, carbon, nitrogen indistinguishable. This leads to ambiguity rotamer protonation states multiple amino acids, notably asparagine, glutamine, histidine, serine, tyrosine, threonine. When residues changes, so too does electrochemical surface a binding site. A variety computational...
Recently much effort has been invested in using convolutional neural network (CNN) models trained on 3D structural images of protein-ligand complexes to distinguish binding from non-binding ligands for virtual screening. However, the dearth reliable x-ray structures and affinity data required use constructed datasets training evaluation CNN molecular recognition models. Here, we outline various sources bias one such widely-used dataset, Directory Useful Decoys: Enhanced (DUD-E). We have...
Abstract Serotonin receptors (5-HT 3A R) play a crucial role in regulating gut movement, and are the principal target of setrons, class high-affinity competitive antagonists, used management nausea vomiting associated with radiation chemotherapies. Structural insights into setron-binding poses their inhibitory mechanisms just beginning to emerge. Here, we present high-resolution cryo-EM structures full-length 5-HT R complex palonosetron, ondansetron, alosetron. Each structure reveals...