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Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Photochemistry".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 29815

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Special Issue Editors

Prof. Dr. Tanveer A. Wani

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Guest Editor

Department of Pharmaceutical Chemistry, King Saud University, Riyadh, Saudi Arabia
Interests: binding interaction; protein-ligand interaction; transport protein; fluorescence quenching; molecular docking; molecular dynamic simulation
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Seema Zargar

E-Mail Website
Guest Editor

Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia
Interests: cancer; expression profiling; oxidative stress; molecular docking; plasma protein; binding
Special Issues, Collections and Topics in MDPI journals

Dr. Afzal Hussain

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Guest Editor

Department of Pharmacognosy, King Saud University, Riyadh, Saudi Arabia
Interests: drug development; chromatographic techniques; bioanalytical; novel synthesis of drug
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biological macromolecules interact with each other or ligands to form complexes. Quantifying the binding of chemical entities to a protein is an important early screening step during drug discovery and is of fundamental interest for estimating safety margins during drug development. Since recognition of their importance at the beginning of the 20th century, investigations into binding parameters have received significant attention. Spectroscopy has emerged as an invaluable tool for such studies, proving to be more efficient and cost-effective. A detailed understanding of protein–ligand interactions is therefore central to understanding biology at a molecular level. Moreover, knowledge of the mechanisms responsible for protein–ligand recognition and binding will also facilitate the discovery, design, and development of drugs. Current progress in experimental and computational methods for identifying and characterizing ligand binding sites on protein targets has provided biological insights that are significant for drug discovery.

It is a pleasure to invite you to contribute to this Special Issue of Molecules entitled “Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins”, which will cover the latest research applications in the field. We aim to collect contributions in the form of original research articles and review articles to add new insights into the role of spectroscopic, thermodynamic and molecular docking studies in drug–protein interactions in biological processes.

Prof. Dr. Tanveer A. Wani
Prof. Dr. Seema Zargar
Dr. Afzal Hussain
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

binding interaction
protein–ligand interaction
transport protein
fluorescence quenching
molecular docking
molecular dynamic simulation

Published Papers (13 papers)

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Editorial

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6 pages, 199 KiB

Open AccessEditorial

Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins

by Tanveer A. Wani, Seema Zargar and Afzal Hussain

Molecules 2022, 27(23), 8405; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27238405 - 01 Dec 2022

Cited by 10 | Viewed by 1072

Abstract

Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, constitutes the basis of all processes in living organisms [...] Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

Research

Jump to: Editorial

25 pages, 7690 KiB

Open AccessArticle

Potential Efficacy of β-Amyrin Targeting Mycobacterial Universal Stress Protein by In Vitro and In Silico Approach

by Md Amjad Beg, Shivangi, Obaid Afzal, Md Sayeed Akhtar, Abdulmalik S. A. Altamimi, Afzal Hussain, Md Ali Imam, Mohammad Naiyaz Ahmad, Sidharth Chopra and Fareeda Athar

Molecules 2022, 27(14), 4581; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27144581 - 18 Jul 2022

Cited by 7 | Viewed by 1775

Abstract

The emergence of drug resistance and the limited number of approved antitubercular drugs prompted identification and development of new antitubercular compounds to cure Tuberculosis (TB). In this work, an attempt was made to identify potential natural compounds that target mycobacterial proteins. Three plant extracts (A. aspera, C. gigantea and C. procera) were investigated. The ethyl acetate fraction of the aerial part of A. aspera and the flower ash of C. gigantea were found to be effective against M. tuberculosis H₃₇Rv. Furthermore, the GC-MS analysis of the plant fractions confirmed the presence of active compounds in the extracts. The Mycobacterium target proteins, i.e., available PDB dataset proteins and proteins classified in virulence, detoxification, and adaptation, were investigated. A total of ten target proteins were shortlisted for further study, identified as follows: BpoC, RipA, MazF4, RipD, TB15.3, VapC15, VapC20, VapC21, TB31.7, and MazF9. Molecular docking studies showed that β-amyrin interacted with most of these proteins and its highest binding affinity was observed with Mycobacterium Rv1636 (TB15.3) protein. The stability of the protein-ligand complex was assessed by molecular dynamic simulation, which confirmed that β-amyrin most firmly interacted with Rv1636 protein. Rv1636 is a universal stress protein, which regulates Mycobacterium growth in different stress conditions and, thus, targeting Rv1636 makes M. tuberculosis vulnerable to host-derived stress conditions. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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25 pages, 10074 KiB

Open AccessArticle

Deep Learning and Structure-Based Virtual Screening for Drug Discovery against NEK7: A Novel Target for the Treatment of Cancer

by Mubashir Aziz, Syeda Abida Ejaz, Seema Zargar, Naveed Akhtar, Abdullahi Tunde Aborode, Tanveer A. Wani, Gaber El-Saber Batiha, Farhan Siddique, Mohammed Alqarni and Ashraf Akintayo Akintola

Molecules 2022, 27(13), 4098; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27134098 - 25 Jun 2022

Cited by 21 | Viewed by 4465

Abstract

NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of −42.67 kJ/mol, better than Dabrafenib (−33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein–ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7–Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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20 pages, 5692 KiB

Open AccessArticle

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

by You-Gang Zhang, Xia-Xia Liu, Jian-Cheng Zong, Yang-Teng-Jiao Zhang, Rong Dong, Na Wang, Zhi-Hui Ma, Li Li, Shang-Long Wang, Yan-Ling Mu, Song-Song Wang, Zi-Min Liu and Li-Wen Han

Molecules 2022, 27(13), 4075; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27134075 - 24 Jun 2022

Cited by 3 | Viewed by 1881

Abstract

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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18 pages, 6225 KiB

Open AccessArticle

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

by Mohd Shahnawaz Khan, Majed S. Alokail, Amal Majed H. Alenad, Nojood Altwaijry, Nouf Omar Alafaleq, Abdulaziz Mohammed Alamri and Mubarak Ali Zawba

Molecules 2022, 27(13), 3992; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27133992 - 21 Jun 2022

Cited by 9 | Viewed by 1889

Abstract

Alpha-amylase (α-amylase) is a key player in the management of diabetes and its related complications. This study was intended to have an insight into the binding of caffeic acid and coumaric acid with α-amylase and analyze the effect of these compounds on the formation of advanced glycation end-products (AGEs). Fluorescence quenching studies suggested that both the compounds showed an appreciable binding affinity towards α-amylase. The evaluation of thermodynamic parameters (ΔH and ΔS) suggested that the α-amylase-caffeic/coumaric acid complex formation is driven by van der Waals force and hydrogen bonding, and thus complexation process is seemingly specific. Moreover, glycation and oxidation studies were also performed to explore the multitarget to manage diabetes complications. Caffeic and coumaric acid both inhibited fructosamine content and AGE fluorescence, suggesting their role in the inhibition of early and advanced glycation end-products (AGEs). However, the glycation inhibitory potential of caffeic acid was more in comparison to p-coumaric acid. This high antiglycative potential can be attributed to its additional –OH group and high antioxidant activity. There was a significant recovery of 84.5% in free thiol groups in the presence of caffeic acid, while coumaric attenuated the slow recovery of 29.4% of thiol groups. In vitro studies were further entrenched by in silico studies. Molecular docking studies revealed that caffeic acid formed six hydrogen bonds (Trp 59, Gln 63, Arg 195, Arg 195, Asp 197 and Asp 197) while coumaric acid formed four H-bonds with Trp 59, Gln 63, Arg 195 and Asp 300. Our studies highlighted the role of hydrogen bonding, and the ligands such as caffeic or coumaric acid could be exploited to design antidiabetic drugs. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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21 pages, 54552 KiB

Open AccessArticle

Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management

by Amany Belal, Mohamed A. Elanany, Eman Y. Santali, Ahmed A. Al-Karmalawy, Moustafa O. Aboelez, Ali H. Amin, Magda H. Abdellattif, Ahmed B. M. Mehany and Hazem Elkady

Molecules 2022, 27(11), 3584; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27113584 - 02 Jun 2022

Cited by 31 | Viewed by 2016

Abstract

Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both the MMP-2 and MMP-9 proteins to find the most promising inhibitors as a proposed computational mechanism to treat keratoconus. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, and MMP inhibitors (MMPIs) are usually designed to interact with zinc ion in the catalytic (CAT) domain, thus interfering with enzymatic activity. In our research work, the FDA-approved ophthalmic medications will be investigated as MMPIs, to explore if they can be repurposed for KC treatment. The obtained findings of the docking study suggest that atenolol and ampicillin are able to accommodate into the active sites of MMP-2 and MMP-9. Additionally, both exhibited binding modes similar to inhibitors used as references, with an ability to bind to the zinc of the CAT. Molecular dynamic simulations and the MM-GBSA binding free-energy calculations revealed their stable binding over the course of 50 ns. An additional pharmacophoric study was carried out on MMP-9 (PDB ID: 1GKC) using the co-crystallized ligand as a reference for the future design and screening of the MMP-9 inhibitors. These promising results open the door to further biological research to confirm such theoretical results. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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13 pages, 5380 KiB

Open AccessArticle

Enhancement of Haloperidol Binding Affinity to Dopamine Receptor via Forming a Charge-Transfer Complex with Picric Acid and 7,7,8,8-Tetracyanoquinodimethane for Improvement of the Antipsychotic Efficacy

by Abdulhakeem S. Alamri, Majid Alhomrani, Walaa F. Alsanie, Hussain Alyami, Sonam Shakya, Hamza Habeeballah, Abdulwahab Alamri, Omar Alzahrani, Ahmed S. Alzahrani, Heba A. Alkhatabi, Raed I. Felimban, Abdulhameed Abdullah Alhabeeb, Bassem M. Raafat, Moamen S. Refat and Ahmed Gaber

Molecules 2022, 27(10), 3295; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27103295 - 20 May 2022

Cited by 13 | Viewed by 1607

Abstract

Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor–acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor–ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL–dopamine. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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20 pages, 5025 KiB

Open AccessArticle

Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes

by Walaa F. Alsanie, Abdulhakeem S. Alamri, Hussain Alyami, Majid Alhomrani, Sonam Shakya, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Ahmed S. Alzahrani, Abdulhameed Abdullah Alhabeeb, Bassem M. Raafat, Moamen S. Refat and Ahmed Gaber

Molecules 2022, 27(10), 3290; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27103290 - 20 May 2022

Cited by 11 | Viewed by 1348

Abstract

The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7′,8,8′-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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19 pages, 4197 KiB

Open AccessArticle

Biophysical, Biochemical, and Molecular Docking Investigations of Anti-Glycating, Antioxidant, and Protein Structural Stability Potential of Garlic

by Mohd W. A. Khan, Ahmed A. Otaibi, Abdulmohsen K. D. Alsukaibi, Eida M. Alshammari, Salma A. Al-Zahrani, Subuhi Sherwani, Wahid A. Khan, Ritika Saha, Smita R. Verma and Nessar Ahmed

Molecules 2022, 27(6), 1868; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27061868 - 14 Mar 2022

Cited by 6 | Viewed by 2444

Abstract

Garlic has been reported to inhibit protein glycation, a process that underlies several disease processes, including chronic complications of diabetes mellitus. Biophysical, biochemical, and molecular docking investigations were conducted to assess anti-glycating, antioxidant, and protein structural protection activities of garlic. Results from spectral (UV and fluorescence) and circular dichroism (CD) analysis helped ascertain protein conformation and secondary structure protection against glycation to a significant extent. Further, garlic showed heat-induced protein denaturation inhibition activity (52.17%). It also inhibited glycation, advanced glycation end products (AGEs) formation as well as lent human serum albumin (HSA) protein structural stability, as revealed by reduction in browning intensity (65.23%), decrease in protein aggregation index (67.77%), and overall reduction in cross amyloid structure formation (33.26%) compared with positive controls (100%). The significant antioxidant nature of garlic was revealed by FRAP assay (58.23%) and DPPH assay (66.18%). Using molecular docking analysis, some of the important garlic metabolites were investigated for their interactions with the HSA molecule. Molecular docking analysis showed quercetin, a phenolic compound present in garlic, appears to be the most promising inhibitor of glucose interaction with the HSA molecule. Our findings show that garlic can prevent oxidative stress and glycation-induced biomolecular damage and that it can potentially be used in the treatment of several health conditions, including diabetes and other inflammatory diseases. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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17 pages, 3482 KiB

Open AccessArticle

Biochemical and Biophysical Characterisation of the Hepatitis E Virus Guanine-7-Methyltransferase

by Preeti Hooda, Mohd Ishtikhar, Shweta Saraswat, Pooja Bhatia, Deepali Mishra, Aditya Trivedi, Rajkumar Kulandaisamy, Soumya Aggarwal, Manoj Munde, Nemat Ali, Abdullah F. AlAsmari, Mohd A. Rauf, Krishna K. Inampudi and Deepak Sehgal

Molecules 2022, 27(5), 1505; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27051505 - 23 Feb 2022

Cited by 7 | Viewed by 2377

Abstract

Hepatitis E virus (HEV) is an understudied pathogen that causes infection through fecal contaminated drinking water and is prominently found in South Asian countries. The virus affects ~20 million people annually, leading to ~60,000 infections per year. The positive-stranded RNA genome of the HEV genotype 1 has four conserved open reading frames (ORFs), of which ORF1 encodes a polyprotein of 180 kDa in size, which is processed into four non-structural enzymes: methyltransferase (MTase), papain-like cysteine protease, RNA-dependent RNA polymerase, and RNA helicase. MTase is known to methylate guanosine triphosphate at the 5′-end of viral RNA, thereby preventing its degradation by host nucleases. In the present study, we cloned, expressed, and purified MTase spanning 33–353 amino acids of HEV genotype 1. The activity of the purified enzyme and the conformational changes were established through biochemical and biophysical studies. The binding affinity of MTase with magnesium ions (Mg²⁺) was studied by isothermal calorimetry (ITC), microscale thermophoresis (MST), far-UV CD analysis and, fluorescence quenching. In summary, a short stretch of nucleotides has been cloned, coding for the HEV MTase of 37 kDa, which binds Mg²⁺ and modulate its activity. The chelation of magnesium reversed the changes, confirming its role in enzyme activity. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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15 pages, 3048 KiB

Open AccessArticle

Interaction Characterization of a Tyrosine Kinase Inhibitor Erlotinib with a Model Transport Protein in the Presence of Quercetin: A Drug–Protein and Drug–Drug Interaction Investigation Using Multi-Spectroscopic and Computational Approaches

by Tanveer A. Wani, Mohammed M. Alanazi, Nawaf A. Alsaif, Ahmed H. Bakheit, Seema Zargar, Ommalhasan Mohammed Alsalami and Azmat Ali Khan

Molecules 2022, 27(4), 1265; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27041265 - 14 Feb 2022

Cited by 37 | Viewed by 2074

Abstract

The interaction between erlotinib (ERL) and bovine serum albumin (BSA) was studied in the presence of quercetin (QUR), a flavonoid with antioxidant properties. Ligands bind to the transport protein BSA resulting in competition between different ligands and displacing a bound ligand, resulting in higher plasma concentrations. Therefore, various spectroscopic experiments were conducted in addition to in silico studies to evaluate the interaction behavior of the BSA-ERL system in the presence and absence of QUR. The quenching curve and binding constants values suggest competition between QUR and ERL to bind to BSA. The binding constant for the BSA-ERL system decreased from 2.07 × 10⁴ to 0.02 × 10² in the presence of QUR. The interaction of ERL with BSA at Site II is ruled out based on the site marker studies. The suggested Site on BSA for interaction with ERL is Site I. Stability of the BSA-ERL system was established with molecular dynamic simulation studies for both Site I and Site III interaction. In addition, the analysis can significantly help evaluate the effect of various quercetin-containing foods and supplements during the ERL-treatment regimen. In vitro binding evaluation provides a cheaper alternative approach to investigate ligand-protein interaction before clinical studies. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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13 pages, 5024 KiB

Open AccessArticle

Mechanistic Insight into Binding of Huperzine A with Human Serum Albumin: Computational and Spectroscopic Approaches

by Anas Shamsi, Moyad Shahwan, Mohd Shahnawaz Khan, Fahad A. Alhumaydhi, Suliman A. Alsagaby, Waleed Al Abdulmonem, Bekhzod Abdullaev and Dharmendra Kumar Yadav

Molecules 2022, 27(3), 797; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030797 - 25 Jan 2022

Cited by 16 | Viewed by 2808

Abstract

Human serum albumin (HSA) is the most abundant protein in plasma synthesized by the liver and the main modulator of fluid distribution between body compartments. It has an amazing capacity to bind with multiple ligands, offering a store and transporter for various endogenous and exogenous compounds. Huperzine A (HpzA) is a natural sesquiterpene alkaloid found in Huperzia serrata and used in various neurological conditions, including Alzheimer’s disease (AD). This study elucidated the binding of HpzA with HSA using advanced computational approaches such as molecular docking and molecular dynamic (MD) simulation followed by fluorescence-based binding assays. The molecular docking result showed plausible interaction between HpzA and HSA. The MD simulation and principal component analysis (PCA) results supported the stable interactions of the protein–ligand complex. The fluorescence assay further validated the in silico study, revealing significant binding affinity between HpzA and HSA. This study advocated that HpzA acts as a latent HSA binding partner, which may be investigated further in AD therapy in experimental settings. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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18 pages, 44687 KiB

Open AccessArticle

Structural Characterization of Ectodomain G Protein of Respiratory Syncytial Virus and Its Interaction with Heparan Sulfate: Multi-Spectroscopic and In Silico Studies Elucidating Host-Pathogen Interactions

by Abu Hamza, Abdus Samad, Md. Ali Imam, Md. Imam Faizan, Anwar Ahmed, Fahad N. Almajhdi, Tajamul Hussain, Asimul Islam and Shama Parveen

Molecules 2021, 26(23), 7398; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26237398 - 06 Dec 2021

Cited by 4 | Viewed by 2214

Abstract

The global burden of disease caused by a respiratory syncytial virus (RSV) is becoming more widely recognized in young children and adults. Heparan sulfate helps in attaching the virion through G protein with the host cell membrane. In this study, we examined the structural changes of ectodomain G protein (edG) in a wide pH range. The absorbance results revealed that protein maintains its tertiary structure at physiological and highly acidic and alkaline pH. However, visible aggregation of protein was observed in mild acidic pH. The intrinsic fluorescence study shows no significant change in the λ_max except at pH 12.0. The ANS fluorescence of edG at pH 2.0 and 3.0 forms an acid-induced molten globule-like state. The denaturation transition curve monitored by fluorescence spectroscopy revealed that urea and GdmCl induced denaturation native (N) ↔ denatured (D) state follows a two-state process. The fluorescence quenching, molecular docking, and 50 ns simulation measurements suggested that heparan sulfate showed excellent binding affinity to edG. Our binding study provides a preliminary insight into the interaction of edG to the host cell membrane via heparan sulfate. This binding can be inhibited using experimental approaches at the molecular level leading to the prevention of effective host–pathogen interaction. Full article

(This article belongs to the Special Issue Spectroscopic, Thermodynamic and Molecular Docking Studies on Molecular Mechanisms of Drug Binding to Proteins)

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