Subha Kalyaanamoorthy

• PhD
• Professor (Assistant) at University of Waterloo

Objectives Progressive supranuclear palsy (PSP) is a neurodegenerative disease showing pathological tau accumulation in subcortical neurons and glial cells. The human leukocyte antigen (HLA) locus on chromosome 6 is a polymorphic region with complex linkage patterns that has been implicated in several autoimmune and neurological disorders. The HLA...

Protein sequence likelihood models (PSLMs) are an emerging class of self-supervised deep learning algorithms that learn probability distributions over amino acid identities conditioned on structural or evolutionary context. Recently, PSLMs have demonstrated impressive performance in predicting the relative fitness of variant sequences without any t...

Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer’s disease (AD) pathology. Decades of research have shown that tau protein undergoes extensive post-translational modifications (PTMs), which can alter the protein's str...

The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro’s susceptibility to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the me...

The RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (A1) regulates RNA metabolism, which is crucial to maintaining cellular homeostasis. A1 dysfunction mechanistically contributes to reduced cell viability and loss, but molecular mechanisms of how A1 dysfunction affects cell viability and loss, and methodologies to attenuate its dysf...

Alzheimer’s disease (AD) is one of the leading causes of death worldwide, with no definitive diagnosis or known cure. The aggregation of Tau protein into neurofibrillary tangles (NFTs), which contain straight filaments (SFs) and paired helical filaments (PHFs), is a major hallmark of AD. Graphene quantum dots (GQDs) are a type of nanomaterial that...

Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally invo...

Purpose: To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach. Methods: The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structur...

The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted the susceptibility of Mpro to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, t...

Since the initial outbreak in December 2019, the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 3 million deaths worldwide. There is an urgent need for developing a potential therapy against SARS-CoV-2. Exploring the potentials of phytochemicals towards inhibition of SARS-CoV-2 prot...

The development of computational methods has enabled impressive advancements in the drug discovery process. These methods allow us to perform eco-friendly and economical screening of enormous molecular databases in a short time frame. Further, the field has been constantly evolving with the development of new methods and the enhancement of high-per...

Introduction Cannabinoid receptors, CB1 and CB2, are class A G-protein coupled receptors (GPCRs) that are involved in different physiological and pathophysiological roles in humans. Since the medical use of cannabis and cannabis-based molecules are widely , there is a growing interest in understanding their molecular pharmacology against CB1 and CB...

Simple Summary The hnRNP A/B family of proteins (comprised of A1, A2/B1, A3, and A0) contributes to the regulation of the majority of cellular RNAs. Here, we provide a comprehensive overview of what is known of each protein’s functions, highlighting important differences between them. While there is extensive information about A1 and A2/B1, we foun...

The current study describes the construction of various ligand-based machine learning models to be used for drug-repurposing against the family of G-Protein Coupled Receptors (GPCRs). In building these models, we collected > 500,000 data points, encompassing experimentally measured molecular association data of > 160,000 unique ligands against > 25...

Background: Sodium/glucose co-transporter 2 (SGLT2) inhibitors exert robust cardioprotective effects against heart failure in diabetes patients and there is intense interest to identify the underlying molecular mechanisms that afford this protection. As the induction of the late component of the cardiac sodium channel current (late-I Na ) is involv...

The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and there is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (Mpro) enzyme in SARS-CoV-2 can be an ideal drug target due to its crucial role in the viral replication a...

‘PoseFilter’ is a PyMOL plugin that assists in analyses and filtering of docked poses. PoseFilter enables automatic detection of symmetric poses from docking outputs and can be accessed using both graphical user interface and command-line options within the PyMOL program. Two methods of analyses, root mean square deviations (RMSD) and interaction f...

COVID-19 caused by a positive-sense single stranded RNA virus named as severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) triggered the global pandemic. This virus has infected about 10.37 Crores and taken lives of 2.24 Crores people of 213 countries to date. To cope-up this emergency clinical trials are undergoing with some existing drug...

Targeted inhibition of misregulated protein–protein interactions (PPIs) has been a promising area of investigation in drug discovery and development for human diseases. However, many constraints remain, including shallow binding surfaces and dynamic conformation changes upon interaction. A particularly challenging aspect is the undesirable off-targ...

Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cel...

The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and a number of countries are already in the middle of the second wave of infection. There is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (Mpro) enzyme in SARS-CoV...

Off-target interactions of drugs with the human ether-à-go-go related gene 1 (hERG1) channel have been associated with severe cardiotoxic conditions leading to the withdrawal of many drugs from the market over the last decades. Consequently, predicting drug-induced hERG-liability is now a prerequisite in any drug discovery campaign. Understanding t...

Multiple sequence alignments (MSAs) play a pivotal role in studies of molecular sequence data, but nobody has developed a minimum reporting standard (MRS) to quantify the completeness of MSAs in terms of completely specified nucleotides or amino acids. We present an MRS that relies on four simple completeness metrics. The metrics are implemented in...

Multiple sequence alignments (MSAs) play a pivotal role in studies of molecular sequence data, but nobody has developed a minimum reporting standard (MRS) to quantify the completeness of MSAs in terms of completely-specified nucleotides or amino acids. We present an MRS that relies on four simple completeness metrics. The metrics are implemented in...

Background: Human CaV1.2 (hCav1.2), a calcium selective voltage-gated channel, plays important roles in normal cardiac and neuronal functions. Calcium influx and gating mechanisms leading to the activation of hCaV1.2 are critical for its functionalities. Lack of an experimentally resolved structure of hCaV1.2 remains a significant impediment in mo...

The development of new biocatalysts using ancestral sequence reconstruction is reported. When applied to an ω-transaminase, the ancestral proteins demonstrated novel and superior activities with eighty percent of the forty...

Model-based molecular phylogenetics plays an important role in comparisons of genomic data, and model selection is a key step in all such analyses. We present ModelFinder, a fast model-selection method that greatly improves the accuracy of phylogenetic estimates by incorporating a model of rate heterogeneity across sites not previously considered i...

Drug-induced blockade of human ether-a-go-go-related gene (hERG) remains a major impediment in delivering safe drugs to the market. Several drugs have been withdrawn from the market due to their severe cardiotoxic side effects triggered by their off-target interactions with hERG. Thus, identifying the potential hERG blockers at early stages of lead...

The inhibitors of class I histone deacetylases (HDACIs) have gained significant interest in cancer therapeutics. Virtual high throughput screening (vHTS) is one of the popular approaches used in the identification of novel scaffolds of HDACIs. However, an accurate description of ligand-protein flexibilities in the vHTS remains challenging. In this...

Exploring the molecular channels of class I histone deacetylases (HDACs) with buried active sites are important to understand their structures and functionalities. In this work, we perform hybrid classical molecular dynamics and random acceleration molecular dynamics simulations to explore the B3N [i.e., (4-(dimethylamino)N-[7(hydroxyamino)-7-oxohe...

The ever-increasing gap between the availabilities of the genome sequences and the crystal structures of proteins remains one of the significant challenges to the modern drug discovery efforts. The knowledge of structure-dynamics-functionalities of proteins is important in order to understand several key aspects of structure-based drug discovery, s...

The effects of different protonation states of the hydroxamic acid (HA) inhibitors against the class I histone deacetylase enzymes (HDACs) have been studied using the state of the art quantum polarized ligand docking (QPLD) and molecular mechanics-generalized Born surface area (MM-GBSA) approaches. The binding modes of the inhibitors and their inte...

Histone deacetylases (HDACs) are important class of enzymes that deacetylate the ε-amino group of the lysine residues in the histone tails to form a closed chromatin configuration resulting in the regulation of gene expression. Inhibition of these HDACs enzymes have been identified as one of the promising approaches for cancer treatment. The type-s...

Molecular channel exploration perseveres to be the prominent solution for eliciting structure and accessibility of active site and other internal spaces of macromolecules. The volume and silhouette characterization of these channels provides answers for the issues of substrate access and ligand swapping between the obscured active site and the exte...

Several technology-based strategies have been developed to address the significance of the two phases of drug discovery: hit identification and lead identification. Structure-based drug design (SBDD), a method that depends on possessing the knowledge of 3D structures of biological targets, is growing swiftly with the development of new technologies...

Glioma, the common brain tumor, which arises from the glial cells, offers worse prognosis and therapy than any other tumors. Despite the genetic and pathological diversities of malignant gliomas, common signaling pathways that drive cellular proliferation, survival, invasion and angiogenesis have been identified. Very often, various tyrosine kinase...

Unlabelled: The advent of genomic and proteomic technologies in this post-genomic era has urged the researchers to develop novel research strategies against cancer by targeting the human genes that would greatly facilitate to identify more promising treatment and to develop accurate early diagnosis for cancer. To harness the power of cancer geneti...

AIM-BLAST, AJAX Interfaced Multisequence Blast, is a simplifi ed tool developed to facilitate the multiple sequences blast using AJAX as an interface. This tool has been integrated with the SOAP services of EBI NCBI Blast and the functionality of AJAX (Asynchronous Javascript and XML), so as to minimize the enormous bandwidth consumption while carr...

Bioinformatics applications are generally multi-server dependants and will have to communicate several information repositories to carry out any analyses. These applications remain computationally intensive and time consuming as they engage lots of data transfer. Hence they face a major bottleneck when ported as web applications. Browser based web...

Histone Deacetylase (HDAC) inhibitors represent a budding class of targeted anti-cancer agents. This structurally diverse group of molecules can induce growth arrest, differentiation, apoptosis, and autophagocytic cell death of cancer cells. Of the different classes of HDAC the class I and Class II are considered the main targets for cancer. For th...