Illustrious Implications of Nature-Inspired Computing Methods in Therapeutics and Computer-Aided Drug Design

Ahmad, Shaban; Sheikh, Kayenat; Bano, Nagmi; Rafeeq, Misbahuddin M; Mohammed, Mohammed Razeeth Shait; Yadav, Manoj Kumar; Raza, Khalid

doi:10.1007/978-981-19-6379-7_15

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…It is essential to underscore that, while this conceptual approach holds promise, rigorous experimental validation is imperative before any drug can be considered for clinical application. Developing effective cancer treatments requires a thorough understanding of the intricate molecular mechanisms involved and the careful consideration of potential side effects and long-term efficacy [ 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Structure-Based In Silico Approaches Reveal IRESSA as a Multitargeted Breast Cancer Regulatory, Signalling, and Receptor Protein Inhibitor

Almasoudi,

Mashraqi,

Alshamrani

et al. 2024

Pharmaceuticals

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Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from −4.527 to −8.809 Kcal/mol and MM/GBSA scores between −49.09 and −61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA’s role.

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Section: Introductionmentioning

confidence: 99%

Structure-Based In Silico Approaches Reveal IRESSA as a Multitargeted Breast Cancer Regulatory, Signalling, and Receptor Protein Inhibitor

Almasoudi,

Mashraqi,

Alshamrani

et al. 2024

Pharmaceuticals

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“…By doing so, multitargeted drugs have the potential to enhance treatment efficacy and overcome resistance mechanisms. Within the multifaceted realm of lung cancer, proteins are critical players in maintaining cellular integrity and suppressing tumour growth [ 21 , 22 , 23 , 24 ]. These proteins are critical regulators of various cellular processes and are intricately involved in tumour suppression mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid’s Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations

Hakami,

Hazazi,

Albloui

et al. 2024

IJMS

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Lung cancer is a pervasive and challenging disease with limited treatment options, with global health challenges often present with complex molecular profiles necessitating the exploration of innovative therapeutic strategies. Single-target drugs have shown limited success due to the heterogeneity of this disease. Multitargeted drug designing is imperative to combat this complexity by simultaneously targeting multiple target proteins and pathways, which can enhance treatment efficacy and overcome resistance by addressing the dynamic nature of the disease and stopping tumour growth and spread. In this study, we performed the molecular docking studies of Drug Bank compounds with a multitargeted approach against crucial proteins of lung cancer such as heat shock protein 5 (BIP/GRP78) ATPase, myosin 9B RhoGAP, EYA2 phosphatase inhibitor, RSK4 N-terminal kinase, and collapsin response mediator protein-1 (CRMP-1) using HTVS, SP with XP algorithms, and poses were filtered using MM\GBSA which identified [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BenCarMethIn YlPro-Phosphonic Acid) (DB02504) as multitargeted drug candidate with docking and MM\GBSA score ranges from −5.83 to −10.66 and −7.56 to −50.14 Kcal/mol, respectively. Further, the pharmacokinetic and QM-based DFT studies have shown complete acceptance results, and interaction fingerprinting reveals that ILE, GLY, VAL, TYR, LEU, and GLN were among the most interacting residues. The 100 ns MD simulation in the SPC water model with NPT ensemble showed stable performance with deviation and fluctuations <2 Å with huge interactions, making it a promising multitargeted drug candidate; however, experimental studies are needed before use.

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“…The EGFR signalling can activate downstream kinases, including CDK2 and IGF-1R, leading to cell cycle progression and growth. Some lung cancer subtypes may exhibit multiple proteins or pathway alterations simultaneously, necessitating a multi-targeted therapeutic approach [ 20 , 21 ]. Understanding the complex network of proteins and signalling pathways involved in lung cancer is crucial for developing effective treatments and personalized medicine approaches [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Unrevealing the multitargeted potency of 3-1-BCMIYPPA against lung cancer structural maintenance and suppression proteins through pharmacokinetics, QM-DFT, and multiscale MD simulation studies

Alshehri,

Asiri,

Helmi

et al. 2024

PLoS ONE

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Lung cancer, a relentless and challenging disease, demands unwavering attention in drug design research. Single-target drugs have yielded limited success, unable to effectively address this malignancy’s profound heterogeneity and often developed resistance. Consequently, the clarion call for lung cancer drug design echoes louder than ever, and multitargeted drug design emerges as an imperative approach in this landscape, which is done by concurrently targeting multiple proteins and pathways and offering a beacon of hope. This study is focused on the multitargeted drug designing approach by identifying drug candidates against human cyclin-dependent kinase-2, SRC-2 domains of C-ABL, epidermal growth factor and receptor extracellular domains, and insulin-like growth factor-1 receptor kinase. We performed the multitargeted molecular docking studies of Drug Bank compounds using HTVS, SP and XP algorithms and poses filter with MM\GBSA against all proteins and identified DB02504, namely [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BCMIYPPA) as multitargeted lead with docking and MM\GBSA score range from -8.242 to -6.274 and -28.2 and -44.29 Kcal/mol, respectively. Further, the QikProp-based pharmacokinetic computations and QM-based DFT showed acceptance results against standard values, and interaction fingerprinting reveals that THR, MET, GLY, VAL, LEU, GLU and ASP were among the most interacting residues. The NPT ensemble-based 100ns MD simulation in a neutralised state with an SPC water model has also shown a stable performance and produced deviation and fluctuations <2Å with huge interactions, making it a promising multitargeted drug candidate—however, experimental studies are suggested.

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Illustrious Implications of Nature-Inspired Computing Methods in Therapeutics and Computer-Aided Drug Design

Cited by 7 publications

References 35 publications

Structure-Based In Silico Approaches Reveal IRESSA as a Multitargeted Breast Cancer Regulatory, Signalling, and Receptor Protein Inhibitor

Structure-Based In Silico Approaches Reveal IRESSA as a Multitargeted Breast Cancer Regulatory, Signalling, and Receptor Protein Inhibitor

Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid’s Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations

Unrevealing the multitargeted potency of 3-1-BCMIYPPA against lung cancer structural maintenance and suppression proteins through pharmacokinetics, QM-DFT, and multiscale MD simulation studies

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