scholarly journals Covalent Docking Predicts Substrates for Haloalkanoate Dehalogenase Superfamily Phosphatases

Biochemistry ◽  
2015 ◽  
Vol 54 (2) ◽  
pp. 528-537 ◽  
Author(s):  
Nir London ◽  
Jeremiah D. Farelli ◽  
Shoshana D. Brown ◽  
Chunliang Liu ◽  
Hua Huang ◽  
...  
Keyword(s):  
Covalent Docking ◽  
Haloalkanoate Dehalogenase

scholarly journals Toward the Identification of Potential α-Ketoamide Covalent Inhibitors for SARS-CoV-2 Main Protease: Fragment-Based Drug Design and MM-PBSA Calculations

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1004
Author(s):  
Mahmoud A. El Hassab ◽  
Mohamed Fares ◽  
Mohammed K. Abdel-Hamid Amin ◽  
Sara T. Al-Rashood ◽  
Amal Alharbi ◽  
...  
Keyword(s):  
Drug Design ◽  
Active Site ◽  
Binding Free Energy ◽  
Stable Complex ◽  
Active Site Residues ◽  
Structure Based Drug Design ◽  
Enzyme Active Site ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Covalent Docking

Since December 2019, the world has been facing the outbreak of the SARS-CoV-2 pandemic that has infected more than 149 million and killed 3.1 million people by 27 April 2021, according to WHO statistics. Safety measures and precautions taken by many countries seem insufficient, especially with no specific approved drugs against the virus. This has created an urgent need to fast track the development of new medication against the virus in order to alleviate the problem and meet public expectations. The SARS-CoV-2 3CL main protease (Mpro) is one of the most attractive targets in the virus life cycle, which is responsible for the processing of the viral polyprotein and is a key for the ribosomal translation of the SARS-CoV-2 genome. In this work, we targeted this enzyme through a structure-based drug design (SBDD) protocol, which aimed at the design of a new potential inhibitor for Mpro. The protocol involves three major steps: fragment-based drug design (FBDD), covalent docking and molecular dynamics (MD) simulation with the calculation of the designed molecule binding free energy at a high level of theory. The FBDD step identified five molecular fragments, which were linked via a suitable carbon linker, to construct our designed compound RMH148. The mode of binding and initial interactions between RMH148 and the enzyme active site was established in the second step of our protocol via covalent docking. The final step involved the use of MD simulations to test for the stability of the docked RMH148 into the Mpro active site and included precise calculations for potential interactions with active site residues and binding free energies. The results introduced RMH148 as a potential inhibitor for the SARS-CoV-2 Mpro enzyme, which was able to achieve various interactions with the enzyme and forms a highly stable complex at the active site even better than the co-crystalized reference.

scholarly journals Molecular Determinants of the Neurotoxicity of Acrylamide Through Covalent Docking

2021 ◽  
Vol 120 (3) ◽  
pp. 123a-124a
Author(s):  
Nicolas P. Müller ◽  
Mercedes Alfonso Prieto
Keyword(s):  
Molecular Determinants ◽  
Covalent Docking

Performance of a 2-haloalkanoate dehalogenase immobilized in a hollow fiber reactor

1989 ◽  
Vol 11 (11) ◽  
pp. 725-729 ◽  
Author(s):  
Pilar Estrada Diaz ◽  
Paul J. Sallis ◽  
Alan W. Bunch ◽  
Alan T. Bull ◽  
David J. Hardman
Keyword(s):  
Hollow Fiber ◽  
Hollow Fiber Reactor ◽  
Haloalkanoate Dehalogenase

Weakly Non-Covalent Docking of Amino-Acid Schiff Base Zn(II) Complex to Lysozyme

2021 ◽  
Vol 888 ◽  
pp. 105-110
Author(s):  
Takashiro Akitsu ◽  
Yuto Kuroda ◽  
Shintaro Suda ◽  
Tetsundo Furuya ◽  
Tomoyuki Haraguchi ◽  
...  
Keyword(s):  
Schiff Base ◽  
Amino Acid ◽  
Synthesis Method ◽  
Low Molecular Weight ◽  
Egg White Lysozyme ◽  
Weight Protein ◽  
Covalent Docking ◽  
Low Molecular Weight Protein ◽  
Catalytic Reactivity ◽  
Amino Acid Schiff Base

Artificial metal enzymes that combine proteins with synthesized unnatural metal complexes as cofactors are attracting attention. The preparation of artificial metal enzymes not only clarifies the behavior of metal ions in biology, but also leads to the development of synthetic chemistry fields such as the discovery of new catalytic reactivity and substrate selectivity that are not observed in nature. In addition, a certain Schiff base zinc (II) complex is known to exhibit antioxidant and anticancer activity, too. Therefore, in this study, we investigated a rapid synthesis method of two known amino acid Schiff base zinc (II) complexes using microwave method and the complexation of zinc (II) complex with chicken egg white lysozyme, which is a relatively low molecular weight protein. Furthermore, investigation of weakly non-covalent intermolecular interaction features between the zinc (II) complexes and lysozyme was also carried out using some spectroscopic measurements.

scholarly journals Covalent docking of large libraries for the discovery of chemical probes

2014 ◽  
Vol 10 (12) ◽  
pp. 1066-1072 ◽  
Author(s):  
Nir London ◽  
Rand M Miller ◽  
Shyam Krishnan ◽  
Kenji Uchida ◽  
John J Irwin ◽  
...  
Keyword(s):  
Chemical Probes ◽  
Covalent Docking

scholarly journals Exploring Covalent Docking Mechanisms of Boron-Based Inhibitors to Class A, C and D β-Lactamases Using Time-dependent Hybrid QM/MM Simulations

2021 ◽  
Vol 8 ◽  
Author(s):  
Łukasz Charzewski ◽  
Krystiana A. Krzyśko ◽  
Bogdan Lesyng
Keyword(s):  
Molecular Modeling ◽  
Rational Design ◽  
Structural Changes ◽  
Molecular Design ◽  
Time Dependent ◽  
Molecular Medicine ◽  
Great Promise ◽  
Resistant Bacteria ◽  
Biological Targets ◽  
Covalent Docking

Recently, molecular covalent docking has been extensively developed to design new classes of inhibitors that form chemical bonds with their biological targets. This strategy for the design of such inhibitors, in particular boron-based inhibitors, holds great promise for the vast family of β-lactamases produced, inter alia, by Gram-negative antibiotic-resistant bacteria. However, the description of covalent docking processes requires a quantum-mechanical approach, and so far, only a few studies of this type have been presented. This study accurately describes the covalent docking process between two model inhibitors - representing two large families of inhibitors based on boronic-acid and bicyclic boronate scaffolds, and three β-lactamases which belong to the A, C, and D classes. Molecular fragments containing boron can be converted from a neutral, trigonal, planar state with sp2 hybridization to the anionic, tetrahedral sp3 state in a process sometimes referred to as morphing. This study applies multi-scale modeling methods, in particular, the hybrid QM/MM approach which has predictive power reaching well beyond conventional molecular modeling. Time-dependent QM/MM simulations indicated several structural changes and geometric preferences, ultimately leading to covalent docking processes. With current computing technologies, this approach is not computationally expensive, can be used in standard molecular modeling and molecular design works, and can effectively support experimental research which should allow for a detailed understanding of complex processes important to molecular medicine. In particular, it can support the rational design of covalent boron-based inhibitors for β-lactamases as well as for many other enzyme systems of clinical relevance, including SARS-CoV-2 proteins.

scholarly journals In silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19

2021 ◽  
Vol 7 ◽  
Author(s):  
Divya M. Teli ◽  
Mamta B. Shah ◽  
Mahesh T. Chhabria
Keyword(s):  
Binding Free Energy ◽  
Treatment Options ◽  
Natural Compounds ◽  
Pharmacokinetic Parameters ◽  
Main Protease ◽  
Glide Docking ◽  
Docking Approach ◽  
Covalent Docking ◽  
Dual Inhibitors ◽  
Potential Inhibitors

Historically, plants have been sought after as bio-factories for the production of diverse chemical compounds that offer a multitude of possibilities to cure diseases. To combat the current pandemic coronavirus disease 2019 (COVID-19), plant-based natural compounds are explored for their potential to inhibit the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the cause of COVID-19. The present study is aimed at the investigation of antiviral action of several groups of phytoconstituents against SARS-CoV-2 using a molecular docking approach to inhibit Main Protease (Mpro) (PDB code: 6LU7) and spike (S) glycoprotein receptor binding domain (RBD) to ACE2 (PDB code: 6M0J) of SARS-CoV-2. For binding affinity evaluation, the docking scores were calculated using the Extra Precision (XP) protocol of the Glide docking module of Maestro. CovDock was also used to investigate covalent docking. The OPLS3e force field was used in simulations. The docking score was calculated by preferring the conformation of the ligand that has the lowest binding free energy (best pose). The results are indicative of better potential of solanine, acetoside, and rutin, as Mpro and spike glycoprotein RBD dual inhibitors. Acetoside and curcumin were found to inhibit Mpro covalently. Curcumin also possessed all the physicochemical and pharmacokinetic parameters in the range. Thus, phytochemicals like solanine, acetoside, rutin, and curcumin hold potential to be developed as treatment options against COVID-19.

Optimization of covalent docking for organophosphates interaction with Anopheles acetylcholinesterase

2021 ◽  
pp. 108054
Author(s):  
Thankhoe A. Rants'o ◽  
C. Johan van der Westhuizen ◽  
Robyn L. van Zyl
Keyword(s):  
Covalent Docking
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