An Analysis of Protein Interaction and Its Methods, Metabolite Pathway and Drug Discovery
Ayodeji Olalekan Salau, Shruti Jain, Meenakshi Sood in Computational Intelligence and Data Sciences, 2022
Docking use to conform ligand binding to the receptor; usually, the receptor is bigger than the molecules. This information includes the coordination of the ligand atoms, to find the lowest energy binding site of the docking configuration. FLEX and AutoDock example programs will be shown in a later chapter of this chapter. The aim is to confirm the binding affinity and the bind. The overall minimum energy of complex formation can be found with the exact position and direction of the binding ligand that belongs to the interacting molecule activation within that. Various bioinformatics tools are helpful in disease management, diagnosis and drug discovery. Sequencing enables identifying the disease and drug discovery by scientists. Mutation and drug and all identified and experimented by utilizing different computational tools. Drug targets decide the suitable drug entry into the pipeline of drug development with the help of bioinformatics tools. The process of designing a medication with the target molecule is known as drug designing. The smallest molecule is ligand that switches on the biological target molecule output in the therapeutic effect [50]. However, the approach of single regulatory is a difficult task in marketing authorization application in all countries. Figure 13.5 represents the levels of drug discovery with regulations. Figure 13.6 shows the drug designing methods and their types.
Heterocyclic Drugs from Plants
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
The smallest ring for a heterocyclic moiety can be of three-membered where at least one heteroatom must be a ring-constituent. Three-membered heterocycles should be more reactive due to angle strain and subsequent steric and torsional strains which taken together is known as ring strain. Angle strain is generated due to distortion of the bonds from a regular tetrahedral angle (109°28′) whereas electronic repulsion between the covalent bonds (bonding electrons) generates torsional strain. Alternatively, if the functional groups or atoms are too close to obscure one another, a strain is generated, called steric strain. The strains of a ligand are crucial to bind a protein/enzyme in the human body. The three strains are present in a three-membered ring. There is no specific limit of ring-size and it can be from three- to nine-membered or even larger rings and fused rings are also possible. The ring constituents in a heterocyclic scaffold can be of any non-carbon elements except the alkali metals.
Overview of Techniques for Direct Measurement of Receptor-Ligand Interactions
John C. Matthews in Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
The third consideration is the affinity of the radiolabeled ligand for the receptor. The lower the affinity the higher the concentrations of ligand required for the binding measurement. The higher the concentration of ligand employed in a receptor binding measurement the larger the proportion of NSB in the total ligand bound. Since NSB is generally unsaturable the amount bound continues to increase as the ligand concentration increases. As is often the case with receptor sites of interest, the concentration of receptors may be very low. When this is true, and when the radioligand is of low affinity, a high concentration of ligand will be required to obtain a measurable fractional receptor occupancy. Under these circumstances the amount of specific ligand bound can become a very small fraction of the total ligand bound. Situations where NSB is 90 or 99% of total binding are easily encountered. Such conditions render the ligand useless for binding measurements since the inherent measurement error will be larger than the specific bound fraction. Some decrease of NSB and increase in receptor concentrations can be accomplished by purification of the receptor. The gains available through such approaches are limited.
Da-Yuan-Yin decoction polyphenol fraction attenuates acute lung injury induced by lipopolysaccharide
Published in Pharmaceutical Biology, 2023
Lengqiu Guo, Yun Yang, Jie Yuan, Huiling Ren, Xiaolei Huang, Meng Li, Long Xia, Xiaogang Jiang, Daofeng Chen, Jian Zhang
The top ten target proteins with degree values were downloaded from the PDB database, and the AutoDock Vina software was used to calculate the minimum binding energy of the compound and target protein and drew a heat map. The affinity energy is a prerequisite indicator to determine whether the ligand small molecule can effectively bind to the receptor, with lower energy values suggesting the better binding capacity for the receptor and ligand. In this study, the lowest binding energy between the compounds and the top 10 target proteins with degree values was mostly less than −5 kal/mol, indicating that they could bind well. PyMoL was used to visualize the molecular docking results (Figure 11). The target protein was closely bound to the active component by hydrogen bond, aromatic interaction and other energetic molecular interactions, further demonstrating that the active component and target protein could form a relatively stable conformation and thus combine well.
Radio-protective efficacy of Gymnema sylvestre on Pangasius sutchi against gamma (60Co) irradiation
Published in International Journal of Radiation Biology, 2022
Pamela Sinha, Kantha Devi Arunachalam, Santhosh Kumar Nagarajan, Thirumurthy Madhavan, Arumugam R. Jayakumar, Mohamed Saiyad Musthafa
Binding energies in the protein-ligand interactions explains how ligand fits with target protein. Examination of the binding interactions of the ligands helps in elucidating the reasonable and appropriate structural features of ligand which increase the binding affinity and therapeutic efficacy. Hence through in-silico studies it may be concluded that Ami and the phyto-components of GS can be used as a novel drug as radioprotector for protecting DNA from radiation but these phyto-components of GS cannot effective for DNA repair mechanism compare to Ami. Similarly, Vinutha et al. (2015) have mentioned that the P. marsupium on pBR322 plasmid DNA and its in-silico studies showed the components of P. marsupium inhibited p53 protein by binding to Arginine 248 and Arginine 273 amino acid, which revealed that the components of P. marsupium can protect DNA from radiation-induced damage. These reports support the current study on radio-protective efficacy of Ami and phyto-components of GS in P. sutchi which can further lead to the higher studies on animal or human model. In order to validate the docking program followed, we have performed docking of Pifithrin-α (PFT-α) hydrobromide with p53 structure 1TUP. PFT-α hydrobromide is a p53 inhibitor which blocks the activation of transcription and apoptosis by p53. We have observed that PFT-α hydrobromide docked in the same binding space as that of other ligands.
Optimum isotherm by linear and nonlinear regression methods for lead (II) ions adsorption from aqueous solutions using synthesized coconut shell–activated carbon (SCSAC)
Published in Toxin Reviews, 2021
Onyedikachi Godwin Okpara, Osareme Mercy Ogbeide, Ozoemena Christain Ike, Kosoluchi Chisom Menechukwu, Eric Chidozie Ejike
The use of synthetic polymeric adsorbent in wastewater treatment has been investigated by several authors (Kunin 1977, Boening et al. 1980, Ferraro 1987, Ezeh et al. 2019), it general efficacy have been demonstrated on various research work which reviewed it applications relative to the basic adsorptive properties. A research work reviewing commercial applications of polymer composites toward improving environmental sustainability by water treatment and desalination has been done (Berber 2020), other related work on Pb (II) ion sorption by semicarbide immobilized polysiloxane has also been done (Ezeh et al. 2019). Other attempts were made to improve synthetic polymeric adsorbent which originally were developed on the basis of ion-exchange resins (Dedek et al. 1992). However, a review of the composition was ascertained to be; synthetic polymer and ligand. Metal ions usually bond to the ligand function to form a coordination complex.
Related Knowledge Centers
- Functional Group
- Molecule
- Coordination Complex
- Ion
- Electron Pair
- Lewis Acids & Bases
- Redox
- Bioinorganic Chemistry
- Medicinal Chemistry
- Homogeneous Catalysis