Joseph Audie

Sacred Heart University · Department of Chemistry

There is controversy surrounding the COVID-19 mortality count in the US. Based on CDC data and standards, published scientific results, expert opinion, and mainstream media reports, a preliminary estimate for COVID-19 deaths caused by or contributed to by SARS-CoV-2 is provided. Future research is needed to refine the estimate and elucidate accurat...

Introduction by Denis G. Rancourt: ---- In this letter to me, Joseph accomplishes the following points: • an explanation of the various kinds of fatality rates for a pathogen • a review of the measured infection fatality rates for SARS-CoV-2 • a demonstration that a recently changed CDC evaluation is most certainly incorrect, along with an illustr...

There is interest in peptide drug design, especially for targeting intracellular protein–protein interactions. Therefore, the experimental validation of a computational platform for enabling peptide drug design is of interest. Here, we describe our peptide drug design platform (CMDInventus) and demonstrate its use in modeling and predicting the str...

Background Increased serum levels of soluble interleukin-2 (IL-2) receptor alpha (sIL-2Rα) are an indicator of poor prognosis in patients with B-cell non-Hodgkin lymphoma (NHL). By binding to IL-2, sIL-2Rα upregulates Foxp3 expression and induces the development of regulatory T (Treg) cells. Methods To inhibit the binding of IL-2 to sIL-2Rα with th...

There is growing interest in peptide-based drug design and discovery. Due to their relatively large size, polymeric nature, and chemical complexity, the design of peptide-based drugs presents an interesting "big data" challenge. Here, we describe an interactive computational environment, PeptideNavigator, for naturally exploring the tremendous amou...

Histidine decarboxylase (HDC) is an enzyme that converts histidine to histamine. Inhibition of HDC has several medical applications, and HDC inhibitors are of considerable interest for the study of histidine metabolism. (S)-α-Fluoromethylhistidine di-hydrochloride (α-FMH) is a potent HDC inhibitor that is commercially available at high cost in smal...

A fundamental and unsolved problem in biophysical chemistry is the development of a computationally simple, physically intuitive and generally applicable method for accurately predicting and physically explaining protein-protein binding affinities from protein-protein interaction (PPI) complex coordinates. Here we propose that the simplification of...

Peptides provide promising templates for developing drugs to occupy a middle space between small molecules and antibodies and for targeting 'undruggable' intracellular protein-protein interactions. Importantly, rational or in cerebro design, especially when coupled with validated in silico tools, can be used to efficiently explore chemical space an...

We have created models to predict cleavage sites for several human proteases including: caspase-1, caspase-3, caspase-6, caspase-7, cathepsin B, cathepsin D, cathepsin G, cathepsin K, cathepsin L, elastase-2, granzyme A, granzyme B, matrix metallopeptidase-2 (MMP2), MMP7, MMP9, thrombin and trypsin-1. Rather than representing the sequence pattern a...

Peptides hold great promise as novel medicinal and biological agents and computational methods can help unlock that promise. In particular, structure-based peptide design can be used to identify and optimize peptide ligands. Successful structure-based design, in turn, requires accurate and fast methods for predicting protein-peptide binding affinit...

Interest in the development of novel peptide-based drugs is growing. There is, thus, a pressing need for the development of effective methods to enable novel peptide-based drug discovery. A cogent case can be made for the development and application of computational or in silico methods to assist with peptide discovery. In particular, there is a ne...

Drug screening targets and method of screening for potential drugs for treatment or amelioration of Alzheimer's Disease are provided.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and that lacks an effective treatment. A biochemical model for neuronal development, recently proposed by Nikolaev et al., that may also have implications for AD, hinges on a novel protein–protein interaction between the death cell recep...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and lacks an effective treatment. A biochemical model for neuronal development that might have implications for AD, recently proposed by Nikolaev and co-workers, hinges on a novel protein-protein interaction between the death cell recept...

The case for peptide-based drugs is compelling. Due to their chemical, physical and conformational diversity, and relatively unproblematic toxicity and immunogenicity, peptides represent excellent starting material for drug discovery. Nature has solved many physiological and pharmacological problems through the use of peptides, polypeptides and pro...

Here we summarize recent work on the continued development of our fast and simple empirical equation for predicting and structurally rationalizing protein-protein and protein-peptide binding affinities. Our empirical expression consists of six regression-weighted physical descriptors and derives from two key simplifying assumptions: (1) the assumpt...

In a previous paper, we described a novel empirical free energy function that was used to accurately predict experimental binding free energies for a diverse test set of 31 protein–protein complexes to within ≈ 1.0 kcal. Here, we extend that work and show that an updated version of the function can be used to (1) accurately predict native binding f...

A free energy function can be defined as a mathematical expression that relates macroscopic free energy changes to microscopic or molecular properties. Free energy functions can be used to explain and predict the affinity of a ligand for a protein and to score and discriminate between native and non-native binding modes. However, there is a natural...