47. Far-UVC (222 nm) Irradiation Effectively Inactivates ssRNA, dsRNA, ssDNA, and dsDNA Viruses as Compared to Germicidal UVC (254 nm), Monika, Santhosh Kumar Madugula, Kiran Kondabagil, Ambarish Kunwar, Photochemistry and Photobiology, DOI: 10.1111/php.13961, Accepted (2024). In this study, the UVC inactivation performances of individual filtered KrCl* excimer lamp (222 nm) and germicidal UVC lamp (254 nm) were determined against four viruses, bacteriophages MS2, Phi6, M13, and T4, having different genome compositions (ssRNA, dsRNA, ssDNA and dsDNA, respectively) and shapes (i.e., spherical (Phi6), linear (M13), and icosahedral (MS2 and T4)). Here, the disinfection efficacies of filtered KrCl* excimer lamp (222 nm) and germicidal UVC lamp (254 nm) were evaluated for highly concentrated virus droplets that mimic the virus-laden droplets released from the infected person and deposited on surfaces as fomites. Filtered KrCl* excimer (222 nm) showed significantly better inactivation against all viruses having different genome compositions and structures compared to germicidal UVC (254 nm).

46. Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations, Aritra Sen, Debashish Chowdhury, Ambarish Kunwar, Advances in Protein Chemistry and Structural Biology, Academic Press (2024), https://doi.org/10.1016/bs.apcsb.2023.12.005. In this article, we illustrate some of the key theoretical approaches used to understand how coordination, cooperation and competition of multiple motors in the crowded intra-cellular environment drive the processes that are essential for biological function of a cell. In spite of the focus on theory, experimentalists will also find this article as an useful summary of the progress made so far in understanding multiple motor systems.

45. 46, XX aromatase deficiency: a single-center experience with the varied spectrum and recurrent variants, and a systematic review of hormonal parameters, Chethan Yami Channaiah, Saba Samad Memon, Vijaya Sarathi, Anurag Ranjan Lila, Rohit Barnabas, Darpan Raghav, Vishwambhar V Bhandare, Sneha Arya, Hemangini Thakkar, Virendra Ashokrao Patil, Manjiri Karlekar, Ambarish Kunwar, Tushar Bandgar, Annales d’Endocrinologie, doi: 10.1016/j.ando.2023.05.010 (2023) Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.

44. Cargo transport properties are enhanced by cylindrical microtubule geometry and elliptical contact zone on cargo surface, Saumya Yadav, Aritra Sen and Ambarish Kunwar, Journal of Theoretical Biology, 565, 111466 (2023) Cargo transport can be modulated by varying various parameters such as cargo size and shape, microtubule geometry, motor number and their arrangement on cargo surface. Only those motors which are present in the contact zone on cargo surface have potential to bind to microtubule. Although earlier studies revealed the importance of cargo size, total motors attached to microtubule and their arrangement on cargo transport, yet how the contact zone influences binding of motors to microtubule largely remains unexplored. Here, it has been shown that contact zone is elliptical in shape for a spherical cargo and increases with cargo size for Kinesin-1 motors. Our findings indicate that cylindrical microtubule geometry maximizes the microtubule-bound motors which enhances the runlength and velocity of cargo transport. Our results show that microtubule-bound motors decrease with cargo size for uniform arrangement of motors on cargo thus decreasing its runlength and velocity, whereas in clustered arrangement, the number of microtubule-bound motors increase with cargo size which leads to increase in runlength and velocity.

43. Computer simulation reveals the effect of severing enzymes on dynamic and stabilized microtubules, Aritra Sen and Ambarish Kunwar, Physical Biology, doi:10.1088/1478-3975/acc301 (2023) Microtubule severing enzymes Katanin and Spastin cut the microtubule (MT) into smaller fragments and are being studied extensively using in-vitro experiments due to their crucial role in different cancers and neurodevelopmental disorders. It has been reported that the severing enzymes are either involved in increasing or decreasing the tubulin mass. In this manuscript, discrete lattice-based Monte Carlo models that included microtubule dynamics and severing enzyme activity have been developed to understand the effect of severing enzymes on tubulin mass, MT number, and MT length. It was found that the action of severing enzyme reduces average MT length while increasing their number; however, the total tubulin mass can decrease or increase depending on the concentration of GMPCPP (Guanylyl-(α, β)-methylene-diphosphonate) – which is a slowly hydrolyzable analogue of GTP (Guanosine triphosphate). Further, relative tubulin mass also depends on the detachment ratio of GTP/GMPCPP and GDP (Guanosine diphosphate) tubulin dimers and the binding energies of tubulin dimers covered by the severing enzyme.

42. Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review, Manjunath Havalappa Dodamani, Anurag Ranjan Lila, Saba Samad Memon, Vijaya Sarathi, Sneha Arya, Ankita Rane, Manjeet Kaur Sehemby, Robin Garg, Vishwambhar Vishnu Bhandare, Manjiri Karlekar, Virendra A Patil, Ambarish Kunwar, Tushar R Bandgar, Calcifed Tissue International, doi:10.1007/s00223-023-01061-8 (2023) Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. In this work, we assessed the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response.

42. Side‐Chain Cleavage Enzyme Deficiency: Systematic Review and Case Series, Aditya Phadte, Sneha Arya, Vijaya SarathiAnurag Lila, Madhur Maheshwari, Sab Samad Memon, Ankita Rane, Virendra Patil, Khushnandan Rai, Darpan Raghav, Ambarish Kunwar, Tushar Bandgar, Clinical Endocrinology, Accepted, doi: 10.1111/cen.14848 (2022) P450 side-chain cleavage deficiency (SCCD) patients present with primary adrenal insufficiency (PAI) with or without undervirilized external genitalia. In this study, we report two new Indian cases of SCCD with three novel likely-pathogenic variants and pubertal follow-up of a previously reported patient.

40. Sliding of motor tails on cargo surface due to drift and diffusion affects their team arrangement and collective transport, Saumya Yadav and Ambarish Kunwar, Physical Biology, 20, 016002 (2022) In this work we use computational models that incorporate random torque, motor torque, and combination of both random and motor torques to understand how they influence the clustering of Kinesin motors on cargo surface due to drift and diffusion of their tails. These studies were performed at varying tail diffusivity to understand their effect on clustering of tails in dispersed and clustered arrangement.

39. Computational study of interactions of anti-cancer drug eribulin with human tubulin isotypes, Khushnandan Rai, Bajarang Vasant Kumbhar, Dulal Panda and Ambarish Kunwar, Physical Chemistry Chemical Physics, 24, 16694-16700 (2022) Microtubules are widely targeted for the treatment of various types of cancer due to their essential role in cell division. This paper presents the study of differential binding affinities of different tubulin isotypes with the potent anti-cancer drug eribulin using computational approaches.

38. Luteinizing hormone β‐subunit deficiency: report of a novel LHB likely pathogenic variant and a systematic review of the published literature, Rohit Barnabas, SwatiRamteke Jadhav, Sneha Arya, Anurag Ranjan Lila, Vijaya Sarathi, Gaurang R Shah, Vishwambhar Vishnu Bhandare, Nalini S Shah, Ambarish Kunwar, Tushar Bandgar, Clinical Endocrinology, Accepted, doi:10.1111/cen.14749 (2022) Selective deficiency of β-subunit of luteinizing hormone (LHB) is a rare disease with scarce data on its characteristics. This study provides description of a male patient with LHB deficiency and a systematic review of LHB deficiency patients published to date.

37. Madhur Maheshwari, Sneha Arya, Anurag Ranjan Lila, Vijaya Sarathi, Rohit Barnabas, Khushnandan Rai, Vishwambhar Vishnu Bhandare, Saba Samad Memon, Manjiri Pramod Karlekar, Virendra Patil, Nalini S Shah, Ambarish Kunwar, Tushar Bandgar, 17α-hydroxylase/17,20-lyase deficiency in 46, XY: our experience and review of literature, Journal of the Endocrine Society,  6 , bvac011 (2022) Pathogenic variants in CYP17A1 that have been identified in patients with 17α-hydroxylase/17,20-lyase defi­ciency (17OHD). Molecular modeling was done for pathogenic variants found in the patients to understand the new interactions in the reported variants.

36. Brijesh Krishnappa, Sneha Arya, Anurag R Lila, Vijaya Sarathi, Saba Samad Memon, Rohit Barnabas, Bajarang Vasant Kumbhar, Vishwambhar Vishnu Bhandare, Virendra Patil, Nalini S Shah, Ambarish Kunwar, Tushar Bandgar, 17β hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: our experience and a gender role-focused systematic review, Clinical Endocrinology, 97, 43–51 (2022) The aim of this manuscript was to describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency

35. Virendra A Patil, Anurag Ranjan Lila, Nalini Shah, Alka V Ekbote, Ravikumar Shah, Vishwambhar Vishnu Bhandare, Vijaya Sarathi, Sneha Arya, Saba Samad Memon, Ambarish Kunwar, Tushar Bandgar, GNRH1 Variants in Congenital Hypogonadotropic Hypogonadism: Single-center experience and Systematic Literature Review, Neuroendocrinology, 112, 723-732 (2022) In this paper, a retrospective study of GNRH1 mutation-positive patients as well as review of published literature of all GNRH1 mutation-positive patients worldwide was carried out. The structure of the human GnRH receptor (GnRHR) was generated by homology modeling and the variant GnRH1 (p.Gln24Leu) structure was generated using the molecular modeling tool.  Molecular docking as well as MD simulations were carried out to understand the effect variant on binding affinity.

34. Amit Bhatti, Sangeeta Ravat, Karan Desai, Bipin R. Shekhar, Shyla R. Menon1, Bajarang V. Kumbhar, Ambarish Kunwar, Neeraj Jain, Dhanjit K. Das, Spectrum of Clinical Variability with SEPT9 Gene Mutation in Hereditary Neuralgic Amyotrophy: Understanding the Pathogenesis using Molecular Dynamics Simulation, Neurology India (Accepted) Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominant disorder characterized by episodes of severe pain and amyotrophy affecting the brachial plexus as well as other sites. Mutations in the SEPT9 gene have been identified as genetic abnormality for HNA. Although the genetic mutations are known, their pathogenesis for the causation of this disorder is not exactly elucidated. Genetic analysis has identified the presence of mutation in SEPT9 gene. The same mutation has been identified in 6 affected members of the family. Molecular simulation study has revealed that the mutation has significantly altered the conformation of septin‑9 protein, thereby impairing the microtubule binding and bundling ability

33. Manjunath Havalappa Dodamani, Manjeetkaur Sehemby, Saba Samad Memon, Vijaya Sarathi, Anurag R. Lila, Aaron Chapla, Vishwambhar Vishnu Bhandare, Virendra A. Patil, Nalini S. Shah, Nihal Thomas, Ambarish Kunwar and Tushar R. Bandgar, Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review, Journal of Pediatric Endocrinology and Metabolism, 34, 1505-1513 (2021) Vitamin D dependent rickets type 1 (VDDR1) is a rare disease which happens due to defect in genes encoding 1-α hydroxylase (CYP27B1). In this work structural modeling of Structural modeling of CYP27B1 was done to understand the effect of pathogenic variants on protein stability and flexibility.

32. Sneha Arya, Rohit Barnabas, Anurag Ranjan Lila, Vijaya Sarathi, Saba Samad Memon, Vishwambhar Vishnu Bhandare, Kunal Thakkar, Virendra Patil, Nalini Samir Shah, Ambarish Kunwar, Tushar Bandgar, Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India, Sexual Development, doi: 10.1159/000517763 (2021) The study was aimed at analyzing clinical and hormonal phenotype, and genotype in patients with genetically proven androgen insensitivity syndrome (AIS) from Western India. The structures of human androgen receptor (AR) ligand-binding domain (LBD) and DNA-binding domain (DBD) were modelled as a full-length structure of AR is not yet available.   These modelled structures of LBD and DBD were then used to analyze the structural and functional effects of identified pathogenic as well as likely pathogenic variants in the patients.

31. Soumendu Ghosh and Ambarish Kunwar, Bi-directional traffic of molecular motors in two antiparallel lanes with asymmetric lane changing rates, Physica A, 570, 125779 (2021)
    Inspired by the recent experimental observations on molecular motors accumulating on microtubule filament, we study an open system of two antiparallel lanes totally asymmetric simple exclusion processes (TASEP) in the presence of dynamic roadblocks.

30. Saumya Yadav and Ambarish Kunwar, Temperature dependent Activity of Motor Proteins: Energetics and Their Implications for Collective Behavior, Frontiers in Cell and Developmental Biology, section Membrane Traffic 9:610899. doi: 10.3389/fcell.2021.610899 (2021) Molecular motor proteins are an extremely important component of the cellular transport system that harness chemical energy derived from ATP hydrolysis to carry out directed mechanical motion inside the cells. Transport properties of these motorssuch as processivity, velocity, and their load dependence have been well established through single-molecule experiments. Temperature dependent biophysical propertiesof molecular motors are now being probed using single-molecule experiments. Additionally, the temperature dependent biochemical properties of motors (ATPaseactivity) are probed to understand the underlying mechanisms and their possible implications on the enzymatic activity of motor proteins. These experiments in turnhave revealed their activation energies and how they compare with the thermal energyavailable from the surrounding medium. In this review, we summarize such temperature dependent biophysical and biochemical properties of linear and rotary motor proteinsand their implications for collective function during intracellular transport and cellular movement, respectively.

29. Manjiri Pramod Karlekar, Vijaya Sarathi, Anurag Lila, Khushnandan Rai, Sneha Arya , Vishwambhar V. Bhandare, Sridevi Atluri, Virendra Patil, Swati Ramteke-Jadhav , Nalini S Shah, Ambarish Kunwar, Tushar Bandgar, Expanding genetic spectrum and discriminatory role of steroid profiling by LC-MS/MS in 11β-hydroxylase deficiency, Clinical Endocrinology (Oxf), 94(4):533-543 (2021). doi: 10.1111/cen.14376. 11β-hydroxylase deficiency (11βOHD) is the second most common cause of congenital adrenal hyperplasia (CAH). It is most prevalent in the Middle East and North Africa. It is an autosomal recessive disorder caused by pathogenic variations in CYP11B1. In this work, structural effects of CYP11B1 pathogenic variations in Indian patients with 11β-hydroxylase deficiency (11βOHD) was explored using molecular modeling approach.

28. Sneha Arya, Ankita Tiwari, Anurag Ranjan Lila, Vijaya Sarathi, Vishwambhar V. Bhandare, Bajarang V. Kumbhar, Khushnandan Rai, Ambarish Kunwar, Hemangini Thakkar, Kunal Thakkar, Saba S. Memon, Virendra Patil, Kranti Khadilkar, Swati S Jadhav, Nalini S Shah, Tushar Bandgar, Homozygous p.Val89Leu plays an important pathogenic role in 5α-reductase type 2 deficiency patients with homozygous p.Arg246Gln in SRD5A2, European Journal of Endocrinology, 183, 275-284 (2020). doi: 10.1530/EJE-19-1050. Steroid 5α-reductase 2 (SRD5A2) enzyme deficiency is a rare autosomal recessive disorder of sexual development. In this paper, phenotypes and genotypes in 23 Indian patients with genetically proven steroid 5α-reductase 2 (SRD5A2) deficiency were retrospectively analyzed. comparision of the interactions of the benign, pathogenic and double variants of SRD5A2 enzymes with that of the wild type enzyme were done molecular modeling and molecular dynamics (MD) simulations.

27. Vishwambhar Bhandare, Bajarang Vasant Kumbhar and Ambarish Kunwar, Differential binding affinity of tau repeat region R2 with neuronal specific β-tubulin isotypes, Scientific Reports 9, 10795 (2019) Tau is a microtubule-associated protein whose C-terminal domain consisting of four repeat regions R1, R2, R3 and R4 binds to microtubules to stabilize them. In several neurodegenerative diseases, tau detaches from microtubules to form insoluble aggregates leading to tauopathy. Tubulin isotypes show tissue specific expression as their relative proportion varies significantly in different type of cells. It is also known that tau binds differently to different cell lines and can either promote or demote microtubule polymerization. However, the relative binding affinity of tau to the different β-tubulin isotypes present in different cell lines is completely unknown. Therefore, we studied relative binding affinity of Tau repeat region R2 to neuronal specific tubulin isotypes βI, βIIb, and βIII using molecular modelling approach and found that the order of binding energy of tau with tubulin is βIII > βIIb > βI. Our strategy can be potentially adapted to understand differential binding affinity of tau towards beta tubulin isotypes present in other cell lines.
    
28. Carlos M. Guardia, Raffaella De Pace, Aritra Sen, Amra Saric, Michal Jarnik, David A. Kolin, Ambarish Kunwar, Juan S. Bonifacino, Reversible association with motor proteins (RAMP): A streptavidin-based method to manipulate organelle positioning, PLoS Biology 17(5): e3000279 (2019)
    A new method, named reversible association with motor proteins (RAMP) has been developed and characterized for manipulation of organelle positioning within the cytoplasm. RAMP consists of coexpressing in cultured cells (i) an organellar protein fused to the streptavidin-binding peptide (SBP) and (ii) motor, neck, and coiled-coil domains from a plus-end–directed or minus-end–directed kinesin fused to streptavidin. The SBP–streptavidin interaction drives accumulation of organelles at the plus or minus end of microtubules, respectively. Importantly, competition of the streptavidin–SBP interaction by the addition of biotin to the culture medium rapidly dissociates the motor construct from the organelle, allowing restoration of normal patterns of organelle transport and distribution. A distinctive feature of this method is that organelles initially accumulate at either end of the microtubule network in the initial state and are subsequently released from this accumulation, allowing analyses of the movement of a synchronized population of organelles by endogenous motors.
    
29. Bajarang Vasant Kumbhar, Vishwambhar Bhandare, Dulal Panda and Ambarish Kunwar, Delineating the Interaction of Combretastatin A-4 with αβ tubulin Isotypes present in Drug Resistant Human Lung Carcinoma using a Molecular Modeling Approach, Journal of Biomolecular Structure and Dynamics.DOI: 10.1080/07391102.2019.1577174 (2019)
    Tubulin isotypes are known to regulate microtubule dynamic instability and contribute to the development of drug resistance in certain types of cancers. Combretastatin-A4 (CA-4) has apotent anti-mitotic, vascular disrupting and anti-angiogenic activity. It binds at the interface of αβ tubulin heterodimers and inhibits microtubules assembly. Interestingly, the CA-4 resistant human lung carcinoma shows alteration of βI and βIII isotype levels, a higher expression of βI tubulin isotype and a decreased expression of βIII tubulin isotypes has been reported in drug resistant cell lines. However, the origin of CA-4 resistance in lung carcinoma is not well understood. Our results suggest that drug resistance is induced in human lung carcinoma cells by altering the expression of β-tubulin isotypes namely βI and βIII which show lowest binding affinities. Our present study can help in designing potential CA-4 analogs against drug-resistant cancer cells showing altered expression of tubulin isotypes.
    
30. Bajarang Vasant Kumbhar, Dulal Panda and Ambarish Kunwar, Interaction of microtubule depolymerizing agent indanocine with different human αβ tubulin isotypes, PLoS ONE 13(3): e0194934 (2018)
    2015 Journal Impact Factor = 3.057
    Tubulin isotypes are known to regulate the stability and dynamics of microtubules, and are also involved in the development of resistance against microtubule-targeted cancer drugs. Indanocine, a potent microtubule depolymerizing agent, is highly active against multidrug-resistant (MDR) cancer cells without affecting normal cells. It is known to disrupt microtubule dynamics in cells and induce apoptotic cell death. Indanocine is reported to bind to tubulin at the colchicine site i.e. at the interface of αβ tubulin heterodimer. However, it’s precise binding mode, involved molecular interactions and the binding affinities with different αβ-tubulin isotypes present in MDR cells are not well understood. Here, the binding affinities of human αβ-tubulin isotypes with indanocine were examined, employing the molecular modeling approach i.e. docking, molecular dynamics simulation and binding energy calculations. Our study provides a significant understanding of involved molecular interactions of indanocine with tubulin isotypes, which may help to design potent indanocine analogues for specific tubulin isotypes in MDR cells in future.
    
31. Anjneya Takshak, Tanushree Roy, Parag Tandaiya and Ambarish Kunwar, Effect of Fuel Concentration and Force on Collective Transport by a Team of Dynein Motors, Protein Science, Vol. 26, 186–197 (2017)
    2015 Journal Impact Factor = 3.039
    Motor proteins are essential components of intracellular transport inside eukaryotic cells. These protein molecules use chemical energy obtained from hydrolysis of ATP to produce mechanical forces required for transporting cargos inside cells, from one location to another, in a directed manner. Of these motors, cytoplasmic dynein is structurally more complex than other motor proteins involved in intracellular transport, as it shows force and fuel (ATP) concentration dependent step-size. Cytoplasmic dynein motors are known to work in a team during cargo transport and force generation. Here, we use a complete Monte-Carlo model of single dynein constrained by in-vitro experiments, which includes the effect of both force and ATP on stepping as well as detachment of motors under force. We then use our complete Monte-Carlo model of single dynein motor to understand collective cargo transport by a team of dynein motors, such as dependence of cargo travel distance and velocity on applied force and fuel concentration.
    
32. Anjneya Takshak, Nirvantosh Mishra, Aditi S Kulkarni, Ambarish Kunwar, Effect of Fuel Concentration on Cargo Transport by a Team of Kinesin Motors, Physica A, Vol. 467, 395–406 (2017)
    2015 Journal Impact Factor = 1.785
    Eukaryotic cells employ specialized proteins called molecular motors for transporting organelles and vesicles from one location to another in a regulated and directed manner. These molecular motors often work collectively in a team while transporting cargos. Molecular motors use cytoplasmic ATP as fuel, which is hydrolyzed to generate mechanical force. While the effect of ATP concentration on cargo transport by single Kinesin motor function is well understood, it is still unexplored, both theoretically and experimentally, how ATP concentration would affect cargo transport by a team of Kinesin motors. For instance, how does fuel concentration affect the travel distances and travel velocities of cargo? How cooperativity of Kinesin motors engaged on a cargo is affected by ATP concentration? To answer these questions, here we develop mechano-chemical models of cargo transport by a team of Kinesin motors. Our new results can be potentially useful in controlling artificial nano-molecular shuttles precisely for targeted delivery in various nano-technological applications.
    
33. Rajan Kumar Pandey, Bajrang Vashant Kumbhar, Shyam Sundar, Ambarish Kunwar and Vijay Kumar Prajapati, Structure based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogues as potential inhibitor against Leishmania donovani trypanothione reductase, Journal of Receptors and Signal Transduction, Vol. 37, 60-70 (2017)
    2015 Journal Impact Factor = 1.782
    Visceral leishmaniasis (VL) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. Increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and pentamidine has been reported in the VL endemic region. To control the VL infection in the affected countries, it is necessary to develop new antileishmanial compounds with high efficacy and negligible toxicity. Computer aided programs such as binding free energy estimation; ADMET prediction and molecular dynamics simulation can be used to investigate novel antileishmanial molecules in shorter duration. In this study, we performed virtual screening of 1,160 benzoxaborole analogues along with reference inhibitors against trypanothione reductase of Leishmania parasite to develop anti-leishmanial lead molecule. The presented drug discovery based on computational study confirm that BOB27 can be used as a potential drug candidate and warrants further experimental investigation to fight against VL in endemic areas.
    
34. Rajan Kumar Pandey, Bajarang Vasant Kumbhar, Shubham Srivastava, Ruchi Malik, Shyam Sundar, Ambarish Kunwar and Vijay Kumar Prajapati, Febrifugine analogues as Leishmaniadonovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation, Journal of Biomolecular Structure and Dynamics, Vol. 35, 141-158 (2017)
    2015 Journal Impact Factor = 2.300
    Visceral leishmaniasis (VL) affects people from 70 countries worldwide, mostly from Indian, African and south American continent. The increasing resistance to antimonial, miltefosine and frequent toxicity of amphotericin B drives an urgent need to develop an antileishmanial drug with excellent efficacy and safety profile. In this study we used molecular docking, ADMET and molecular dynamics simulation to confirm that that 6-chloro-3-[3-(3-hydroxy-2-piperidyl)-2-oxo-propyl]-7-(4-pyridyl) quinazolin-4-one can be potential drug candidate to fight against Leishmaniadonovani parasites.
    
35. Weili Hong, Anjneya Takshak, Olaolu Osunbayo, Ambarish Kunwar and Michael Vershinin, The Effect of Temperature on Microtubule-Based Transport by Cytoplasmic Dynein and Kinesin-1 Motors, Biophysical Journal, Vol. 111, 1287 (2016)
    2015 Journal Impact Factor = 3.632
    Cytoplasmic dynein and kinesin are both microtubule-based molecular motors but are structurally and evolutionarily unrelated. Under standard conditions, both move with comparable unloaded velocities toward either the microtubule minus (dynein) or plus (most kinesins) end. This similarity is important because it is often implicitly incorporated into models that examine the balance of cargo fluxes in cells and into models of the bidirectional motility of individual cargos. We examined whether this similarity is a robust feature, and specifically whether it persists across the biologically relevant temperature range. The velocity of mammalian cytoplasmic dynein, but not of mammalian kinesin-1, exhibited a break from simple Arrhenius behavior below 15°C—just above the restrictive temperature of mammalian fast axonal transport. In contrast, the velocity of yeast cytoplasmic dynein showed a break from Arrhenius behavior at a lower temperature (∼8°C). Our studies implicate cytoplasmic dynein as a more thermally tunable motor and therefore a potential thermal regulator of microtubule-based transport. Our theoretical analysis further suggests that motor velocity changes can lead to qualitative changes in individual cargo motion and hence net intracellular cargo fluxes.
    
36. Bajarang Vasant Kumbhar, Anubhaw Borogaon, Dulal Panda and Ambarish Kunwar, Exploring the Origin of Differential Binding Affinities of Human Tubulin Isotypes αβII, αβIII and αβIV for DAMA-colchicine using Homology Modelling, Molecular Docking and Molecular Dynamics Simulation, PLoS ONE 11(5): e0156048 (2016)
    2015 Journal Impact Factor = 3.057
    Tubulin isotypes are found to play an important role in regulating microtubule dynamics. The isotype composition is also thought to contribute in the development of drug resistance as tubulin isotypes show differential binding affinities for various anti-cancer agents. Tubulin isotypes αβII, αβIII and αβIV show differential binding affinity for colchicine. However, the origin of differential binding affinity is not well understood at the molecular level. In this paper, we investigate the origin of differential binding affinity of a colchicine analogue N-deacetyl-N-(2-mercaptoacetyl)-colchicine (DAMA-colchicine) for human αβII, αβIII and αβIV isotypes, employing sequence analysis, homology modeling, molecular docking, molecular dynamics simulation and MM-GBSA binding free energy calculations. Our computational approaches provide an insight into the effect of residue variations on differential binding of αβII, αβIII and αβIV tubulin isotypes with DAMA-colchicine and may help to design new analogues with higher binding affinities for tubulin isotypes.
    
37. Hanumant Pratap Singh, Anjneya Takshak, Utkarsh Mall and Ambarish Kunwar, Sliding of Microtubules by A Team of Dynein motors: Understanding the Effect of Spatial Distribution of Motor Tails and Mutual Exclusion of Motor Heads on Microtubules, International Journal of Modern Physics C, Vol. 27, 1650137 (2016)
    2015 Journal Impact Factor = 1.195
    Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. Here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distribution of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.
    
38. Anjneya Takshak and Ambarish Kunwar, Importance of anisotropy in detachment rates for force production and cargo transport by a team of motor proteins, Protein Science, Vol. 25, 1075 (2016)
    2015 Journal Impact Factor = 3.039
    Many cellular processes are driven by collective forces generated by a team consisting of multiple molecular motor proteins. One aspect that has received less attention is the detachment rate of molecular motors under mechanical force/load. While detachment rate of kinesin motors measured under backward force increases rapidly for forces beyond stall-force; this scenario is just reversed for non-yeast dynein motors where detachment rate from microtubule decreases, exhibiting a catch-bond type behavior. It has been shown recently that yeast dynein responds anisotropically to applied load i.e. detachment rates are different under forward and backward pulling. Here, we use computational modeling to show that these anisotropic detachment rates might help yeast dynein motors to improve their collective force generation in the absence of catch-bond behavior. We further show that the travel distance of cargos would be longer if detachment rates are anisotropic. Our results suggest that anisotropic detachment rates could be an alternative strategy for motors to improve the transport properties and force production by the team.
    
39. Aijaz Rashid , Annapurna Kuppa , Ambarish Kunwar and Dulal Panda, Thalidomide (5HPP-33) suppresses microtubule dynamics and depolymerizes microtubule network by binding at vinblastine binding site on tubulin, Biochemistry, Vol. 54, 2149 (2015)
    2015 Journal Impact Factor = 2.876
    Thalidomides were initially thought to be broad range drugs specially to cure insomnia and to relieve morning sickness in pregnant women. However, its use was discontinued because of a major drawback of causing teratogenicity. In this study, we found that a thalidomide derivative, (5-hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione) (5HPP-33) inhibited the proliferation of MCF-7. 5HPP-33 depolymerized microtubules and inhibited the reassembly of cold-depolymerized microtubules in MCF-7 cells. Molecular docking analysis suggested that 5HPP-33 shares its binding site on tubulin with vinblastine. The results provide a significant insight into the anti-mitotic mechanism of action of 5HPP-33 and also suggest a possible mechanism for the teratogenicity of thalidomides.
    
40. Roop Mallik, Arpan Kumar Rai, Pradeep Barak, Ashim Rai and Ambarish Kunwar, Teamwork in Microtubule Motors, Trends in Cell Biology,Vol. 23, 575 (2013)
    2015 Journal Impact Factor = 11.532
    Collective forces generated by a team consisting of multiple motor proteins drive diverse cellular processes. Here we review how the biophysical properties of single motors, and differences therein, may translate into collective motor function during organelle transport and perhaps in other processes outside transport.
    
41. Jubina Balan Venghateri, Tilak Kumar Gupta, Paul J Verma, Ambarish Kunwar and Dulal Panda, Ansamitocin P3 depolymerizes microtubules and induces apoptosis by binding to tubulin at the vinblastine site, PLoS ONE 8(10): e75182. doi:10.1371/journal.pone.0075182 (2013)
    2012 Journal Impact Factor = 3.057
    In this paper, we have elucidated the mechanism of action of ansamitocin P3, a structural analogue of maytansine for its anticancer activity. Ansamitocin P3 potently inhibited the proliferation of MCF-7, HeLa, EMT-6/AR1 and MDA-MB-231 cells in culture. Ansamitocin P3 strongly depolymerized both interphase and mitotic microtubules and perturbed chromosome segregation at its proliferation inhibitory concentration range. Treatment of ansamitocin P3 activated spindle checkpoint surveillance proteins, Mad2 and BubR1 and blocked the cells in mitotic phase of the cell cycle. The binding of ansamitocin P3 induced conformational changes in tubulin. A docking analysis suggested that ansamitocin P3 may bind partially to vinblastine binding site on tubulin in two different positions.
    
42. Ankit Rai, Tilak Kumar Gupta, Sudarshan Kini, Ambarish Kunwar, Avadhesha Surolia, Dulal Panda, CXI-benzo-84 reversibly binds to tubulin at colchicine site and induces apoptosis in cancer cells, Biochemical Pharmacology, Vol. 86, 378 (2013)
    2015 Journal Impact Factor = 5.091
    In this paper, we discovered that CXI-benzo-84 is a potential anticancer agent from a library of benzimidazole derivatives using cell based screening strategy. CXI-benzo-84 inhibited cell cycle progression in metaphase stage of mitosis and accumulated spindle assembly checkpoint proteins Mad2 and BubR1 on kinetochores, which subsequently activated apoptotic cell death in cancer cells. CXI-benzo-84 depolymerized both interphase and mitotic microtubules, perturbed EB1 binding to microtubules and inhibited the assembly and GTPase activity of tubulin in vitro. Competition experiments and molecular docking suggests that CXI-benzo-84 binds to tubulin at the colchicine-site.

___________________________Publications before Joining IIT Bombay__________________________

11. Ambarish Kunwar, Suvranta K Tripathy, Jing Xu, Michelle K. Mattson, Preetha Anand, Roby Sigua, Michael Vershinin, Richard J. McKenney, Clare C. Yu, Alexander Mogilner†, Steven P. Gross†, Mechanical Stochastic Tug-of-war Models Cannot Explain Bi-directional Lipid droplet Transport, Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, 18960 (2011). *,† Equal Authorship
    2011 Journal Impact Factor = 9.681
    Experiments suggest that both kinesin and dynein motors have a catch-bond type behavior. Stochastic model predicts correct average detachment time for multiple kinesin and dynein motors. Comparison of theoretical modeling with experiments suggests mechanistic tug-of-war scenarios are inconsistent with observed motion for bi-directional lipid droplet motion.
    
12. Richard J. McKenney, Michael Vershinin, Ambarish Kunwar, Richard B. Vallee† and Steven P. Gross†, LIS1 and NudE Induce a Persistent Dynein Force-Producing State, Cell, Vol. 141, 304 (2010).*,† Equal authorship. On Cover of Cell-April 16, 2010 issue.
    2011 Journal Impact Factor = 32.403
    Investigates the function of dynein in presence of Lis1 and NudE. NudE alone both recruits dynein to a particular location, but also inactivates it. Lis1 then binds NudE, and the combined Dynein-NudE-Lis1 complex is again active, but now with improved performance. The Dynein-NudE-Lis1 complexes has higher processivity and lower detachment rate under load. This allows each dynein motors to remain attached to the microtubule for longer period under load, which in turn allows multiple motors to work more effectively. In the presence of Lis1 and NudE, the same number of motors can exert a higher average force, not because each motor exerts more force, but rather because on average more motors remain attached to the microtubule.
    
13. Ambarish Kunwar and Alexander Mogilner, Robust Transport by Multiple Motors with Non-linear Force-Velocity Relations and Stochastic Load Sharing, Physical Biology, Vol. 7, 016012 (2010).
    2011 Journal Impact Factor = 2.595
    Investigates properties of multiple motor based transport, using both stochastic and mean-field model of load sharing, for motor having non-linear force-velocity curves.

8. Ambarish Kunwar, Michael Vershinin, Jing Xu and Steven P. Gross, Stepping, Strain Gating, and an Unexpected Force-Velocity Curve for Multiple-Motor-Based Transport, Current Biology, Vol. 18, 1173 (2008).
   2011 Journal Impact Factor = 9.647
   Proposes a stochastic model of load sharing to theoretically investigate how multiple kinesin motors work together. Modeling shows how unequal/stochastic load sharing can result in enhanced performance of multiple motors under load. It also shows that multiple motor function depends strongly on the coupling between individual motors. It also predicts that, surprisingly, for a range of likely cytosolic viscosities, cargos driven by a single motor can move faster than cargos moved by two or more motors. This prediction was later confirmed experimentally.

___________________________Publications from IIT Kanpur__________________________

7. Ambarish Kunwar, Andreas Schadschneider and Debashish Chowdhury, From aggressive driving to molecular motor traffic, Journal of Physics A: Mathematical and General, Vol. 39, 14263 (2006).
   Name changed to Journal of Physics A: Mathematical and Theoretical in year 2007
   2011 Journal Impact Factor = 1.564
8. Ambarish Kunwar, Debashish Chowdhury, Andreas Schadschneider and Katsuhiro Nishinari, Competition of coarsening and shredding of clusters in a driven diffusive lattice gas, Journal of Statistical Mechanics: Theory and Experiment, P06012 (2006).
   2011 Journal Impact Factor = 1.727
9. Pankaj Kumar Mishra, Ambarish Kunwar, Sutapa Mukherji and Debashish Chowdhury, Dynamic instability of microtubules: effect of catastrophe-suppressing drugs, Physical Review E, Vol. 72, 051914 (2005).
   (Selected for the November 15, 2005, issue of the Virtual Journal of Biological Physics Research)
   2011 Journal Impact Factor = 2.255
10. Dietrich Stauffer, Ambarish Kunwar and Debashish Chowdhury, Evolutionary ecology in-silico: evolving foodwebs, migrating populations and speciation, Physica A: Statistical Mechanics and its Applications, Vol. 352, 202 (2005).
    2011 Journal Impact Factor = 1.373
11. Ambarish Kunwar, Evolution of spatially inhomogeneous eco-systems: An unified model based approach, International Journal of Modern Physics C, Vol. 15, 1449 (2004).
    2011 Journal Impact Factor = 0.570
12. Ambarish Kunwar, Alexandar John, Katshuhiro Nishinari, Andreas Schadschneider and Debashish Chowdhury, Collective traffic-like movement of ants on a trail: Dynamical phases and phase transitions, Journal of the Physical Society of Japan, Vol. 73, 2979 (2004).
    2011 Journal Impact Factor = 2.364
13. Debashish Chowdhury, Dietrich Stauffer and Ambarish Kunwar, Unification of small and large time scales for biological evolution: Deviations from Power law, Physical Review Letters, Vol.90, 068101(2003).
    (Selected for the February 15, 2003, issue of the Virtual Journal of Biological Physics Research)
    2011 Journal Impact Factor = 7.370