Natarajan Arul Murugan

• Ph.D, Docent
• Associate professor at Indraprastha Institute of Information Technology Delhi

Autism Spectrum Disorder (ASD) comprises a myriad of disorders with vast pathologies, aetiologies, and involvement of genetic and environmental risk factors. Given the polygenic aspect of ASD, targeting several genes/proteins responsible for pathogenesis at once might prove advantageous in its remediation. Various phytochemicals have been proven to...

Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60–80 % of all dementia cases. Currently, there are no curative or d...

Here we report a NIR-I emissive optical marker BI-CyG derived from cyanine to trace hepatic albumin variation during hyperglycemia.

Molecular Property Diagnostic Suite (MPDS) was conceived and developed as an open-source disease-specific web portal based on Galaxy. MPDSCOVID-19 was developed for COVID-19 as a one-stop solution for drug discovery research. Galaxy platforms enable the creation of customized workflows connecting various modules in the web server. The architecture...

Background Alzheimer's disease (AD) is the most prevalent dementia, affecting a large number of populations. Despite being under scrutiny for decades, an effective therapeutic option is still not available. Methods and results This study explores the therapeutic role of a nootropic herb Bacopa monnieri (BM) in AD‐like pathological conditions produ...

Cellular genome is considered a dynamic blueprint of a cell since it encodes genetic information that gets temporally altered due to various endogenous and exogenous insults. Largely, the extent of genomic dynamicity is controlled by the trade‐off between DNA repair processes and the genotoxic potential of the causative agent (genotoxins or potenti...

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDS TB )....

GROMACS is one of the most widely used HPC software packages using the Molecular Dynamics (MD) simulation technique. In this work, we quantify GROMACS parallel performance using different configurations, HPC systems, and FFT libraries (FFTW, Intel MKL FFT, and FFT PACK). We break down the cost of each GROMACS computational phase and identify non-sc...

The design of novel fibril imaging molecules for medical diagnosis requires the simultaneous optimization of fibril-specific optical properties and binding specificity toward amyloid fibrils. Because of the possibility to monitor internal organs and deep tissues, the two-photon probes that can absorb in the infrared (IR) and near-IR (NIR) region wi...

Traditionally, the exogenous allosteric modulators of G protein-coupled receptors (GPCRs) have been extensively investigated due to their pharmacological significance. However, to date, only a handful of endogenous intracellular allosteric modulators are known, that too with inconclusive binding information and their associated phenotypes. This lim...

Exogenous allosteric modulators of GPCRs have been extensively investigated. To date, a few endogenous intracellular allosteric modulators are known with inconclusive binding information and their associated phenotypes. This limited understanding stems from the non-availability of robust computational techniques facilitating automated cavity identi...

Correction for ‘Computational investigation of the increased virulence and pathogenesis of SARS-CoV-2 lineage B.1.1.7’ by N. Arul Murugan et al. , Phys. Chem. Chem. Phys. , 2022, 24 , 20371–20380, https://doi.org/10.1039/D2CP00469K.

GROMACS is one of the most widely used HPC software packages using the Molecular Dynamics (MD) simulation technique. In this work, we quantify GROMACS parallel performance using different configurations, HPC systems, and FFT libraries (FFTW, Intel MKL FFT, and FFT PACK). We break down the cost of each GROMACS computational phase and identify non-sc...

New variants of SARS-CoV-2 are being reported worldwide. The World Health Organization has reported Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529) as the variants of concern. There are speculations that the variants might evade the host immune responses induced by currently available vaccines and develop res...

Artificial intelligence (AI)-based computational techniques allow rapid exploration of the chemical space. However, representation of the compounds into computational-compatible and detailed features is one of the crucial steps for quantitative structure–activity relationship (QSAR) analysis. Recently, graph-based methods are emerging as a powerful...

In this study, we investigated differential molecular interactions of crystalline and amorphous forms of telmisartan (TEL), which is a non-peptide angiotensin-II receptor antagonist commonly used in the management of hypertension. Amorphous telmisartan (AM-TEL) was prepared using quench cooling of the melt. The analysis of solid-state properties of...

Exploring the new therapeutic indications of known drugs for treating COVID-19, popularly known as drug repurposing, is emerging as a pragmatic approach especially owing to the mounting pressure to control the pandemic. Targeting multiple targets with a single drug by employing drug repurposing known as the polypharmacology approach may be an optim...

A typical drug discovery project involves identifying active compounds with significant binding potential for selected disease-specific targets. Experimental high-throughput screening (HTS) is a traditional approach to drug discovery, but is expensive and time-consuming when dealing with huge chemical libraries with billions of compounds. The searc...

Exploring the new therapeutic indications of known drugs for treating COVID-19, popularly known as drug repurposing, is emerging as a pragmatic approach especially owing to the mounting pressure to control the pandemic. Targeting multiple targets with a single drug by employing drug repurposing known as the polypharmacology approach may be an optim...

With the promising advantages of the near-infrared region (NIR) emissive markers for serum albumin becoming very prominent recently, we devised CyG-NHS as the cyanine derived longest NIR-I emissive optical marker possessing albumin selective recognition ability in diverse biological milieu. Multiscale modeling involving molecular docking, molecular...

The paradigm of advanced materials has grown exponentially over the last decade, with their new dimensions including digital design, dynamics, and functions. Materials modeling such as that of their properties and behavior in various environments using ab initio approaches, force-field methods and machine learning represents a key step in advanced...

The new variant of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Omicron, has been quickly spreading in many countries worldwide. Compared to the original virus, Omicron is characterized by several mutations in its genomic region, including the spike protein’s receptor-binding domain (RBD). We have computationally investigated...

The current global health emergency in the form of the Coronavirus 2019 (COVID-19) pandemic has highlighted the need for fast, accurate, and efficient drug discovery pipelines. Traditional drug discovery projects relying on in vitro high-throughput screening (HTS) involve large investments and sophisticated experimental set-ups, affordable only to...

We present fluorogenic cationic organo chalcogens that are highly selective to RNA. We have demonstrated that the conformational dynamics and subsequently the optical properties of these dyes can be controlled to facilitate efficient bioimaging. We report the application of organoselenium and organosulfur‐based cell‐permeable red‐emissive probes be...

Drug discovery is the most expensive, time-demanding, and challenging project in biopharmaceutical companies which aims at the identification and optimization of lead compounds from large-sized chemical libraries. The lead compounds should have high-affinity binding and specificity for a target associated with a disease, and, in addition, they shou...

The machine learning (ML) research based on the quantitative structure-property relationship (QSPR) have been applied to the development of high-efficient dye-sensitized solar cells (DSSCs). This study brings forward a robust...

The new variant of SARS-CoV-2, Omicron, has been quickly spreading in many countries worldwide. Compared to the original virus, Omicron is characterized by several mutations in its genomic region, including spike protein's receptor-binding domain (RBD). We have computationally investigated the interaction between RBD of both wild-type and omicron v...

Stereoselectivity is important in many pharmacological processes but its impact on drug membrane transport is scarcely understood. Recent studies showed strong stereoselective effects in the cellular uptake of fenoterol by the organic cation transporters OCT1 and OCT2. To provide possible molecular explanations, homology models were developed and t...

Drug discovery is the most expensive, time demanding and challenging project in biopharmaceutical companies which aims at the identification and optimization of lead compounds from large-sized chemical libraries. The lead compounds should have high affinity binding and specificity for a target associated with a disease and in addition they should h...

To assess a tumor biomarker like the cyclooxygenase-2 enzyme (COX-2), non-invasive imaging techniques are powerful tools. The (non-) linear optical properties of activatable fluorescent probes which are selectively bound to the biomarker can therefore be exploited. The here presented molecular modelling results based on multi-scale modelling techni...

Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and Tau aggregates in the brain, which induces various pathological events resulting in neurodegeneration. There have been continuous efforts to develop modulators of the Aβ and Tau aggregation process to halt or modify disease progression. A few small‐molecule‐based inhi...

COVID-19 is considered as a major public health problem caused by the SARS CoV-2. This Viral infection is known to induce worldwide pandemic in short period of time. Emerging evidence suggested that the transmission control and drug therapy may influence the preventive measures extensively as the host surrounding environment and pathogenic mechanis...

Three types of chemical entities, namely, small organic molecules (organics), peptides, and biologics, are mainly used as drug candidates for the treatment of various diseases. Even though the peptide drugs are known since 1920 in association with the clinical use of insulin, only a limited number of peptides are currently used for therapeutics due...

Tauopathies are a subclass of neurodegenerative diseases characterized by an accumulation of microtubule binding tau fibrils in brain regions. Diseases such as Alzheimer’s (AD), chronic traumatic encephalopathy (CTE), Pick’s disease (PiD), and corticobasal degeneration (CBD) belong to this subclass. Development of tracers which can visualize and di...

The aberrant production, aggregation, and accumulation of parenchymal amyloid‐β (Aβ) is the pathological hallmark of multifaceted Alzheimer's disease (AD) etiology and accounts for neuronal loss, progressive memory impairment, and cognitive decline. An aptly designed small molecule (TGR63) effectively reduced amyloid burden in the brain, rescues ne...

A wide variety of neurodegenerative diseases are characterized by the accumulation of protein aggregates in intraneuronal or extraneuronal brain regions. In Alzheimer’s disease (AD), the extracellular aggregates originate from amyloid-β proteins, while the intracellular aggregates are formed from microtubule-binding tau proteins. The amyloid formin...

Alzheimer's disease (AD) is a major neurodegenerative disorder and the leading cause of dementia worldwide. Predominantly, misfolding and aggregation of amyloid‐β (Aβ) peptides associated with multifaceted toxicity is the neuropathological hallmark of AD pathogenesis and, thus the primary therapeutic target to ameliorate neuronal toxicity and cogni...

New variants of SARS-CoV-2 are being reported worldwide. More specifically, the variants reported in South Africa (501Y.V2) and United Kingdom (B.1.1.7) were found to be more contagious than the wild type. There are also speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistan...

We present here a new insight into the chemical reactivity and bioactivity of dopamine (DA) and gallic acid (GA) and their hyaluronic acid (HA) conjugates. Our data suggest that HA-GA...

Alzheimer's disease (AD) is one of the most devastating diseases that affects the human brain. Currently, there are no potent therapeutic treatments available except for a few FDA approved drugs that are used for treating the symptoms associated with the disease. For diagnostics, there are only a few tracers available for amyloid and tau imaging. W...

Abstract The current outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major threat to human healthcare. The virus has already infected more than 44 M people and the number of deaths reported has reached more than 1.1 M which may be attributed to lack of medicine. The traditional drug discovery appr...

Monoamine oxidase B (MAOB) is expressed in the mitochondrial membrane and has a key role in degrading various neurologically active amines such as benzylamine, phenethylamine and dopamine with the help of Flavin adenine dinucleotide (FAD) cofactor. The Parkinson’s disease associated symptoms can be treated using inhibitors of MAO-B as the dopamine...

Alzheimer's disease (AD) is a major neurodegenerative disorder and the leading cause of dementia worldwide. Predominantly, misfolding and aggregation of amyloid-β (Aβ) peptides associated with multifaceted toxicity is the neuropathological hallmark of AD pathogenesis and thus, primary therapeutic target to ameliorate neuronal toxicity and cognitive...

The monoamine oxidase B (MAO-B) is the potential biomarker for Parkinson's disease (PD), a neurodegenerative disease associated with the loss of motor activities in human subjects. The disease state is associated with dopamine deprival and so the inhibitors of MAO-B can serve as therapeutic drugs for PD. Since the expression level of MAO-B directly...

The selective recognition and imaging of oncogene specific G-quadruplex (GQ) structures holds great promise in the development of diagnostic therapy (theranostics) for cancer and has been challenging due to their structural dynamics and diversity. We report selective recognition of GQ by a small molecule through unique hybrid loop stacking and groo...

Multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for neurodegenerative diseases as they target multiple pathways involved in the progression of these diseases. Herein, we report first-in-class dual inhibitor of acetylcholinesterase (AChE) and tau aggregation as a novel class of multitargeted ligands for neurod...

The prevalence of respiratory illness caused by the novel SARS-CoV-2 associated with multiple organ failures is spreading rapidly due to its contagious human-to-human transmission and inadequate global healthcare systems. Pharmaceutical re-use, reflecting an effective drug development technique using existing drugs, could shorten the time and reduc...

The outbreak due to SARS-CoV-2 (or Covid-19) is spreading alarmingly and number of deaths due to infection is aggressively increasing every day. Due to the rapid human to human transmission of Covid-19, we are in need to find a potent drug at the earliest by ruling-out the traditional time-consuming approach of drug development. This is only possib...

The current outbreak of Covid-19 infection due to SARS-CoV-2, a virus from the coronavirus family, has become a major threat to human healthcare. The virus has already infected more than 5 M people and the number of deaths reported has reached more than 330 K which may be attributed to lack of medicine. The traditional drug discovery approach invol...

Assembly and co-assemblies of peptide amphiphiles through specific noncovalent forces expand the space of molecular architectonics-driven construction of diverse nanoarchitectures with potential biological applications. In this work, cyclic dipeptide amphiphiles (CDPAs) of cyclo(Gly-Asp) with varying lengths of alkyl chains (C8-C18) were synthesize...

Multiple lines of evidence indicate that amyloid beta (Aβ) peptide is responsible for the pathological devastation caused in Alzheimer’s disease (AD). Aβ aggregation species predominantly contribute to multifaceted toxicity observed in neuronal cells including generation of reactive oxygen species (ROS), mitochondrial dysfunction, interfering with...

Abnormal deposition of hyperphosphorylated tau as neurofibrillary tangles (NFTs) is an important pathological hallmark of Alzheimer’s disease (AD) and of other neurodegenerative disorders. A non-invasive positron emission tomography (PET) tracer that quantifies neurofibrillary tangles in vivo can enhance the clinical diagnosis of AD and can also be...

The widespread interest in phase recognition of lipid membranes has led to the use of different optical techniques to enable differentiation of healthy and not fully functional cells. In this work, we show how the combination of different (non)linear optical methods such as One Photon Absorption (OPA), Two Photon Absorption (TPA) and Second Harmoni...

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+) dependent enzymes, which undergo robust deacetylase activity, resulting in the production of nicotinamide. It is well known that nicotinamide which is one of the products, can also acts as an inhibitor for further deacetylation process by forming the NAD+ again. Hence, the removal of...

Purpose Several tracers have been designed for tracking the abnormal accumulation of tau pathology in vivo. Recently, concerns have been raised about the sources of off-target binding for these tracers; inconclusive data propose binding for some tracers to monoamine oxidase B (MAO-B). Methods Molecular docking and dynamics simulations were used to...

A series of novel BF2 complexes, bearing a five-membered heterocyclic ring (with X = NMe, O, and S), were synthesized and characterized with a focus on the influence of atom exchange on the photophysical properties of both unsubstituted and dimethylamino derivatives. The experimental results show that the optical spectra substantially differ in bot...

The present work is motivated by the established concept that the structure and energetics of biomacromolecules can be modulated by confining their dimensions in the nanoscale. In particular, here we use force-field methods to understand the stability of amyloid fibrils at nanostructured interfaces, which can be useful for the development of new th...

To address drug resistance to HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel diarylpyrimidine (DAPY) derivatives targeting “Tolerant Region I” and “Tolerant Region II” of the NNRTIs binding pocket (NNIBP) were designed utilizing a structure-guided scaffold-hopping strategy. The dihydrofuro[3,4-d]pyrimidine derivat...

In recent times, our healthcare system is being challenged by many drug-resistant microorganisms and ageing-associated diseases for which we do not have any drugs or drugs with poor therapeutic profile. With pharmaceutical technological advancements, increasing computational power and growth of related biomedical fields, there have been dramatic in...

Understanding the initial events in aggregation of amyloid beta monomers to form beta sheet rich fibrils is useful to development of therapeutics for Alzheimer’s disease. In this context, the changes in energetics involved in the aggregation of helical amyloid beta monomers into beta sheet rich dimers have been investigated using umbrella sampling...

Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five sub-series of oseltamivir derivatives were designed and synthesized to improve their activity towards drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidase...

Parkinson’s disease (PD) is a serious neurodegenerative disease and is characterized by abnormal α-synuclein (α-syn) accumulation in Lewy bodies (LB) and Lewy neurites (LN), which makes α-syn an important imaging target for PD. An imaging probe that quantifies fibrillar α-syn can enhance the clinical diagnosis of PD and can also be used to evaluate...

Understanding the mechanism of fibrilization of amyloid forming peptides could be useful for the development of therapeutics for Alzheimer disease (AD). Taking this standpoint, we have explored in this work the free energy profile for the inter-conversion of monomeric and dimeric forms of amyloid forming peptides into different secondary structures...

The widespread interest in phase recognition of lipid membranes has led to the use of different optical techniques to enable differentiation of healthy and not fully functional cells. In this work, we show how the combination of different (non-)linear optical methods such as One Photon Absorption (OPA), Two Photon Absorption (TPA) and Second Harmon...

Optical imaging of amyloid fibrils serves as a cost-effective route for the diagnosis of Alzheimer-like conformational diseases. However, the challenge here is to optimize the binding affinity and photophysical properties of the optical imaging agents in a way specific to certain types of amyloids. In a few occasions it is shown that novel optical...

Thanks to the recently reported cryo-EM structure for the tau fibril (Nature 547, 185-190 (2017)) which is a potential target concerning Alzheimer’s disease, we present the first molecular modeling studies on its interaction with various Positron Emission Tomography (PET) tracers. Experimentally, based on the binding assay studies, at least three d...

We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as rigid, flexible or partly-flexible (restrained) body. T...

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide it poses a great challenge for the society and healthcare. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the beta region of the amyloid precursor protein which is r...

Nanomaterials have been at the center of attraction for almost five decades as their contributions to different disciplines such as electronics, photonics and medicine are enormous. Various kinds of nanomaterials have been developed and are currently utilized in innumerable applications. Nevertheless, their simple realization and easy and efficient...

Ambidextrous supergelators are developed through structure-gelation screening of rationally designed cyclic dipeptides (CDPs). The organo- and hydrogels of CDPs were thoroughly characterized by their minimal gelation concentration (MGC) for organic and aqueous solvents, thermal stability (Tg) and visco-elastic properties. Intermolecular hydrogen bo...

The design of inhibitors for human immunodeficiency virus type‐1 reverse transcriptase ( HIV ‐1 RT ) is one of the most successful approaches for the treatment of HIV infections. Among the HIV ‐1 RT inhibitors, non‐nucleoside reverse transcriptase inhibitors ( NNRTIs ) constitute a prominent drug class, which includes nevirapine, delavirdine, efavi...

Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer's disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of β-amyloid (A...

Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely...

Understanding the properties of bitumen and its interaction with mineral aggregates is crucial for future strategies to improve roads and highways. Knowledge of basic molecular and electronic structures of bitumen, one out of the two main components of asphalt, poses a major step towards achieving such a goal. In the present work we employ atomisti...

Thrombin binding aptamer (TBA) that shows anticoagulant properties is one of the most studied G-quadruplex forming aptamers. In this study, we investigated the impact of different chemical modifications such as Spacer-C3, unlocked nucleic acid (UNA) and 3'-amine-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three mod...

The fluorescent marker Laurdan and its new derivative, C-Laurdan, have been investigated by means of theoretical calculations in a DOPC lipid bilayer membrane at room temperature and a comparison is made with results from fluorescence experiments. Experimentally, the latter probe is known to have a higher sensitivity to the membrane polarity at the...

To cope with the rapid evolution of the tissue engineering field, it is now essential to incorporate the use of on-site responsive scaffolds. Therefore, it is of utmost importance to find new ‘Intelligent’ biomaterials that can respond to the physicochemical changes in the microenvironment. In this present report, we have developed biocompatible st...

The engineering of materials with advanced features is driving the research towards the design of innovative materials with high performances. New materials often deliver the best solution for structural applications, precisely contributing towards the finest combination of mechanical properties and low weight. The mimicking of nature's principles...

Positron emission tomography (PET) tracers play an important role in the diagnosis of Alzheimer's disease, a condition that leads to progressive dementia and memory loss. A high binding affinity and specificity of the PET tracers to amyloid oligomers and fibrils are crucial for their successful application as diagnostic agents. In this sense it is...

We study the linear and non-linear optical properties of a well-known acid-base indicator, bromophenol blue (BPB), in aqueous solution by employing static and integrated approaches. In the static approach, optical properties have been calculated using the time-dependent density functional theory (TD-DFT) on the fully relaxed geometries of neutral a...

The design of molecular probes and tracer molecules with specificity towards amyloid-beta fibrils is of paramount importance for the selective diagnosis of Alzheimer's disease. This requires a detailed understanding of the binding sites in amyloid targets, their number and binding mechanism for various tracer molecules. We adopt an integrated appro...