BITS Faculty Publications

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Subject: search.filters.subject.Molecular dynamics simulation (MDS)

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    Discovery of potent DNMT1 inhibitors against sickle cell disease using structural-based virtual screening, MM-GBSA and molecular dynamics simulation-based approaches
    (Taylor & Francis, 2023-04) Murugesan, Sankaranarayanan
    Sickle cell disease (SCD) is an autosomal recessive genetic disorder affecting millions of people worldwide. A reversible and selective DNMT1 inhibitor, GSK3482364, has been known to decrease the overall methylation activity of DNMT1, resulting in the increase of HbF levels and percentage of HbF-expressing erythrocytes in an in vitro and in vivo model. In this study, a structure-based virtual screening was done with GSK3685032, a co-crystalized ligand of DNMT1 (PDB ID: 6X9K) with an IC50 value of 0.036 μM and identified 3988 compounds from three databases (ChEMBL, PubChem and Drug Bank). Using this screening method, we identified around 15 compounds with XP docking scores greater than −8 kcal/mol. Further, prime MM-GBSA calculations have been performed and found compound SCHEMBL19716714 with the highest binding free energy of −83.31 kcal/mol. Finally, four compounds were identified based on glide energy and ΔG bind scores that have the most binding with DG7, DG19, DG20 bases and Lys1535, His1507, Trp1510, Ser1230, which were required for the target enzyme inhibition. Furthermore, molecular dynamics simulation studies of top ligands validate the stability of the docked complexes by examining root mean square deviations, root mean square fluctuations, solvent accessible surface area, and radius of gyration graphs from simulation trajectories. These findings suggest that the top four hit compounds may be capable of inhibiting DNMT1 and that additional in vitro and in vivo studies will be essential to prove the clinical effectiveness of the selected lead compounds.
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    Pharmacoinformatics-Based Approach for Uncovering the Quorum-Quenching Activity of Phytocompounds against the Oral Pathogen, Streptococcus mutans
    (MDPI, 2023-07) Murugesan, Sankaranarayanan
    Streptococcus mutans, a gram-positive oral pathogen, is the primary causative agent of dental caries. Biofilm formation, a critical characteristic of S. mutans, is regulated by quorum sensing (QS). This study aimed to utilize pharmacoinformatics techniques to screen and identify effective phytochemicals that can target specific proteins involved in the quorum sensing pathway of S. mutans. A computational approach involving homology modeling, model validation, molecular docking, and molecular dynamics (MD) simulation was employed. The 3D structures of the quorum sensing target proteins, namely SecA, SMU1784c, OppC, YidC2, CiaR, SpaR, and LepC, were modeled using SWISS-MODEL and validated using a Ramachandran plot. Metabolites from Azadirachta indica (Neem), Morinda citrifolia (Noni), and Salvadora persica (Miswak) were docked against these proteins using AutoDockTools. MD simulations were conducted to assess stable interactions between the highest-scoring ligands and the target proteins. Additionally, the ADMET properties of the ligands were evaluated using SwissADME and pkCSM tools. The results demonstrated that campesterol, meliantrol, stigmasterol, isofucosterol, and ursolic acid exhibited the strongest binding affinity for CiaR, LepC, OppC, SpaR, and Yidc2, respectively. Furthermore, citrostadienol showed the highest binding affinity for both SMU1784c and SecA. Notably, specific amino acid residues, including ASP86, ARG182, ILE179, GLU143, ASP237, PRO101, and VAL84 from CiaR, LepC, OppC, SecA, SMU1784c, SpaR, and YidC2, respectively, exhibited significant interactions with their respective ligands. While the docking study indicated favorable binding energies, the MD simulations and ADMET studies underscored the substantial binding affinity and stability of the ligands with the target proteins. However, further in vitro studies are necessary to validate the efficacy of these top hits against S. mutans.
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    Fluid-structure Interactions and Flow Induced Vibrations: A Review
    (Elsevier, 2016) Parameshwaran, R.
    Fluid-structure interaction (FSI) is intensely coupled with the flow induced vibration (FIV) through the motions induced on a deformable or moving structure being subjected to an external or internal fluid flow. This kind of interaction in turn evolves with a variety of flow phenomena having applications that ranges from aeroelasticity to blood flow through arteries. The prime objective of this paper is to review the potential research studies pertaining to a variety of modelling and computational techniques, dedicated for exploring the underlying physics of the phenomena relating to the fluid structure interactions and the flow induced vibrations. Technical revelations related to the dynamic effects of the flow induced vibrations on engineering systems in fluidic environment have been gleaned from numerous research studies and presented. Emphasis is also given on the fluid flow analysis pertaining to the excitation of low-frequency vibration modes in structures at nanoscale for the efficient design of modern engineering systems.
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    Molecular dynamics simulation of mechanical polishing
    (Inder Science, 2019-07) Sharma, Anuj
    Mechanical polishing, a nano-finishing process is extensively used for generating smooth surfaces on engineering materials. The mechanism of mechanical polishing is extremely complex due to its random nature of material removal at atomic scale. The need for a better understanding of the process at atomic scale is therefore necessary. Hence, molecular dynamics simulation (MDS) was carried out to understand the behaviour of material removal on two different types of engineering materials viz. aluminium and silicon. In the present work, material removal of rough asperities was modelled and simulated by abrading them with abrasive particles. It was observed that the nanometric abrasion occurs through adhesion de-bonding principle, recoverable phase transformation occurs during the nanometric abrasion on aluminium, and the non-crystalline debris formation during polishing of silicon as brittle crystalline structures. In addition, other attributes are also discussed such as force, stress, chemical stability, effect of abrasive particle, and temperature.
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    A molecular dynamics simulation of wear mechanism of diamond tool in nanoscale cutting of copper beryllium
    (Springer, 2019-01) Sharma, Anuj
    In the present study, molecular dynamics simulation (MDS) is employed to study the wear mechanism of single crystal diamond tool during nanocutting of copper beryllium (CuBe). Two edge configurations, i.e., both sharp and worn out tools, are chosen to study the tool and workpiece interaction during the nanocutting of CuBe. Further, the study involves the experimental characterization techniques viz. scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy to confirm the simulation results. The results of the molecular dynamics simulation (MDS) show that the presence of Be as a hard particle in workpiece material influences the cutting forces which subsequently causes degradation of the sharp edge of the diamond tool. Furthermore, the carbon (C) atoms removed from the tool react with Be particles and as a result, it causes the formation of beryllium carbide (BeC). Beryllium interaction with the blunt edge configuration of the tool causes amorphization at the tool edge. Raman spectroscopy of the used diamond tool on CuBe reveals the similar phenomena of amorphization of the diamond at the tool edge. Moreover, surface generation is dependent on the tool edge condition as blunt edge tool leads to smoother surface compared to the surface generated by sharp edge configuration.
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    Investigation of tool-workpiece interaction in nanoscale cutting: a molecular dynamics study
    (Inder Science, 2019) Roy, Tribeni; Sharma, Anuj
    Ductile and brittle materials differ in their physical and mechanical properties and pose distinct interaction with the cutting tool while nano-machining. It is thus imperative to analyse the mechanism of material removal and tool-workpiece interaction. Towards this, molecular dynamics simulation (MDS) is carried out to study the diamond tool and workpiece interaction in the nanoscale cutting of Cu (ductile material) and Si (brittle material). Results show that material removal in Cu takes place through shear deformation by dislocations formation and their propagation while in case of Si, it takes place through phase transformation of the material in cutting zone. Force analysis of both the materials shows that machinability of Cu in nanoscale cutting is better compared to Si. Furthermore, tool wear while machining of Si with sharp edge tool is due to chipping whereas radial distribution function reveals that graphitisation of the round edge tool occurs during machining of Si.
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    Molecular dynamics study on the effect of discharge on adjacent craters on micro EDMed surface
    (Elsevier, 2018-04) Roy, Tribeni; Sharma, Anuj
    Using molecular dynamics simulation (MDS), investigation was carried out to understand the mechanism of material removal during the formation of overlapping craters on surfaces obtained by micro electrical discharge machining (MEDM) and their effect on the crater surface. Apart from overlapping craters, two other cases were also considered viz. craters separated by a finite distance and craters coinciding at the periphery since these two will mostly occur during initial phase of machining. In all cases, the material removal was due to melting and vaporisation; it was also observed that the amount of material removal by vaporisation increased from 36% (approx.) in 1st discharge to 44% (approx.) in the 2nd discharge due to ease of vaporising the amorphous layer formed after the 1st discharge. Moreover, final crater size viz. depth and diameter obtained in the 1st crater measured at the end of MDS was relatively less as compared to 2nd crater. The increase in crater depth and diameter increased with reduction in distance between discharges. The increase in diameter of 2nd crater with respect to 1st crater for all the three cases was observed both during MDS and on the actual surface generated by MEDM.