A5071315709- Ion Channels and Receptors
- Ion channel regulation and function
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Bioactive Compounds and Antitumor Agents
- Genetics, Bioinformatics, and Biomedical Research
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Genomics and Phylogenetic Studies
- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Protein purification and stability
- Nicotinic Acetylcholine Receptors Study
- Mass Spectrometry Techniques and Applications
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Pain Mechanisms and Treatments
- Infectious Encephalopathies and Encephalitis
- Cholinesterase and Neurodegenerative Diseases
- Catalytic C–H Functionalization Methods
- Polydiacetylene-based materials and applications
- Neuroscience and Neural Engineering
- Histone Deacetylase Inhibitors Research
- Menstrual Health and Disorders
Queens College, CUNY
2024
Temple University
2014-2023
Swarthmore College
2020
University of the Sciences
2012-2016
Nerviano Medical Sciences
2005
Influenza virus infections lead to numerous deaths and millions of hospitalizations each year. One challenge facing anti-influenza drug development is the heterogeneity circulating influenza viruses, which comprise several strains with variable susceptibility antiviral drugs. For example, wild-type (WT) A such as seasonal H1N1, tend be sensitive drugs, amantadine rimantadine, while S31N mutant pandemic 2009 H1N1 (H1N1pdm09) H3N2, are resistant this class Thus, drugs targeting both WT highly...
Hv1s are ubiquitous highly selective voltage-gated proton channels involved in male fertility, immunology, and the invasiveness of certain forms breast cancer. The mechanism extrusion Hv1 is not yet understood, while it constitutes first step toward design high-affinity drugs aimed at this important pharmacological target. In contribution, we explore details via an integrative approach, using classical QM/MM molecular dynamics simulations a monomeric hHv1 model. We propose that protons...
Hv1 is a transmembrane four-helix bundle that transports protons in voltage-controlled manner. Its crucial role many pathological conditions, including cancer and ischemic brain damage, makes promising drug target. Starting from the recently solved crystal structure of Hv1, we used structural modeling molecular dynamics simulations to characterize channel's most relevant conformations along activation cycle. We then performed computational docking known inhibitors, 2-guanidinobenzimidazole...
This Perspective outlines recent progress and future directions for using machine learning (ML), a data-driven method, to address critical questions in the design, synthesis, processing, characterization of biomacromolecules. The achievement these tasks requires navigation vast complex chemical biological spaces, difficult accomplish with reasonable speed. Using modern algorithms supercomputers, quantum physics methods are able examine systems containing few hundred interacting species...
The tetrameric M2 proton channel of influenza A virus is an integral membrane protein responsible for the acidification viral interior. Drugs such as amantadine target transmembrane region wild type by acting pore blockers. However, a number mutations affecting this domain confer drug resistance, prompting need alternative inhibitors. availability high-resolution structures drug-bound M2, paired with computational investigations, revealed that inhibitors can bind at different sites, and...
The histone deacetylases (HDACs) are able to regulate gene expression, and deacetylase inhibitors (HDACi) emerged as a new class of agents in the treatment cancer well other human disorders such neurodegenerative diseases. In present investigation, we report on synthesis biological evaluation compounds derived from expansion HDAC inhibitor scaffold having N-hydroxy-3-phenyl-2-propenamide N-hydroxy-3-(pyridin-2-yl)-2-propenamide core structures containing phenyloxopropenyl moiety, either...
Zika virus (ZIKV) infection is associated with microcephaly in neonates and Guillain-Barré syndrome adults. ZIKV produces a class of nonstructural (NS) regulatory proteins that play critical role viral transcription replication, including NS5, which possesses RNA-dependent RNA polymerase (RdRp) activity. Here we demonstrate rilpivirine (RPV), non-nucleoside reverse transcriptase inhibitor (NNRTI) used the treatment HIV-1 infection, inhibits enzymatic activity NS5 suppresses replication...
The transient receptor potential ankyrin 1 (TRPA1) channel functions as an irritant sensor and is a therapeutic target for treating pain, itch, respiratory diseases. As ligand-gated channel, TRPA1 can be activated by electrophilic compounds such allyl isothiocyanate (AITC) through covalent modification or noncovalent agonists ligand binding. However, how leads to opening and, importantly, binding activates are not well-understood. Here we report class of piperidine carboxamides (PIPCs)...
Regulation of the heat- and capsaicin-activated transient receptor potential vanilloid 1 (TRPV1) channel by phosphoinositides is complex controversial. In most recent TRPV1 cryo-EM structure, endogenous phosphatidylinositol (PtdIns) was detected in binding site, were proposed to act as competitive antagonists. This model difficult reconcile with 4,5-bisphosphate [PtdIns(4,5)P2] being a well-established positive regulator TRPV1. Here we show that presence PtdIns(4,5)P2 excised patches,...
The use of small molecule libraries for fragment-based primary screening (FBS) is a well-known approach to identify protein binders in the low affinity range. However, search, analysis, and selection suitable fragments can be lengthy process, because large number compounds that must analyzed different levels ring/substituents identification submitted selection/exclusion criteria based on their physicochemical properties. purpose present work propose strategy substructures from databases...
Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel expressed in peripheral sensory neurons and the central nervous system. TRPM3 activity depends on membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but molecular mechanism of activation by PI(4,5)P2 not known. As no experimental structure available, we built homology model complex with PI(4,5)P2via modeling. We identified putative contact residues for pre-S1 segment, S4-S5 linker,...
Since its introduction in 2003, the Shape Signatures method has been successfully applied a number of drug design projects. Because it uses ray-tracing approach to directly measure molecular shape and properties (as opposed relying on chemical structure), excels at scaffold hopping, is extraordinarily easy use. Despite advantages, significant drawback hampered application certain classes problems; namely, when structures considered are large contain heterogeneous ring-systems, produces...
Prostate Cancer (PCa), a leading cause of cancer death worldwide (www.cancer.gov), is complex malignancy where spectrum targets leads to diversity PCa forms. A widely pursued therapeutic target the Androgen Receptor (AR). As Steroid Hormone Receptor, AR serves as activator transcription upon binding androgens and plays central role in development PCa. structurally flexible protein, conformational plasticity residues binding-pocket key its ability accommodate ligands from various chemical...
ABSTRACT Transient Receptor Potential Melastatin 3 (TRPM3) is a heat-activated ion channel expressed in peripheral sensory neurons and the central nervous system. TRPM3 activity depends on membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ], but molecular mechanism of activation by PI(4,5)P not known. As no experimental structure available, we built homology model complex with via modeling. We identified putative contact residues for pre-S1 segment, S4-S5 linker,...
Abstract PoInTree (Polar and Interactive Tree) is an application that allows to build, visualize, customize phylogenetic trees in a polar, interactive, highly flexible view. It takes as input FASTA file or multiple alignment formats. Phylogenetic tree calculation based on sequence distance method utilizes the Neighbor Joining (NJ) algorithm. also displaying precalculated of major protein families Pfam classification. In PoInTree, nodes can be dynamically opened closed distances between genes...