Evaluation of the hypoglycemic potential of a black bean hydrolyzed protein isolate and its pure peptides using in silico, in vitro and in vivo approaches

The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated long-chain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.

https://www.mdpi.com/1420-3049/23/10/2544/pdf

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells.

Drug designing and molecular dynamic studies were an intense, lengthy and an inter-disciplinary venture. At present, a new approach towards the use of computational chemistry and molecular modeling for in-silico drug design. Computational in-silico drug design skills are used in bioinformatics, computational biology and molecular biology. Drug designing using in-silico methods is cost effective in research and development of drugs. Currently, a vast number of software’s used in drug design. In-silico drug designing and molecular dynamic studies can be performed by using different methods namely homology modeling, molecular dynamic studies, energy minimization, docking and QSAR etc. By using in-silico drug designing we can produce an active lead molecule from the preclinical discovery stage to late stage clinical development. The lead molecules which are developed will help us in selection of only potent leads to cure particular diseases. Therefore in-silico methods have been of great importance in target identification and in prediction of novel drugs.

https://www.longdom.org/open-access/computational-drug-design-and-molecular-dynamic-studiesa-review-2090-4924-1000123.pdf

Computational Drug Design and Molecular Dynamic Studies-A Review

Background: Despite concerted global efforts to combat malaria, malaria elimination is still a remote dream. Fast evolution rate of malarial parasite along with its ability to respond quickly to any drug resulting in partial or complete resistance has been a cause of concern among researcher communities. Materials and Methods: Molecular modeling approach was adopted to gain insight about the structure and various analyses were performed. Modeller 9v3, Protparam, Protscale, MEME, NAMD and other tools were employed for this study. PROCHECK and other tools were used for stereo-chemical quality evaluation. Results and Conclusion: It was observed during the course of study that this protein contains 32.2% of aliphatic amino acids among which Leucine (9.5%) is predominant. Theoretical pI of 8.39 identified the protein as basic in nature and most of the amino acids present in N-Myristoyltransferase are hydrophobic (46.1%). Secondary structure analysis shows predominance of alpha helices and random coils. Motif analyses revealed that this target protein contains 2 signature motifs, i.e., EVNFLCVHK and KFGEGDG. Apart from motif search, three-dimensional model was generated and validated and the stereo-chemical quality check confirmed that 97.7% amino acid residues fall in the core region of Ramachandran plot. Molecular dynamics simulation resulted in maximum 1.3 A Root Mean Square Deviation (RMSD) between the initial structure and the trajectories obtained later on. The template and the target molecule has shown 1.5 A RMSD for the C alpha trace. A docking study was also conducted with various ligand molecules among which specific benzofuran compounds turned out to be effective. This derived information will help in designing new inhibitor molecules for this target protein as well in better understanding the parasite protein.

Analyzing a Potential Drug Target N-Myristoyltransferase of Plasmodium falciparum Through In Silico Approaches

Malaria remains one of the leading causes of deaths attributable to a communicable disease globally. The reemergence of drug-resistant Plasmodium falciparum, the most fatal human malarial parasite, has necessitated the exploration of different pathways to provide the urgently required novel drug targets. Aspartate carbamoyltransferase, an enzyme of de novo pyrimidine biosynthetic pathway in Plasmodium represents an attractive drug target. The enzyme was characterized using in silico tools. Tertiary (3D) structure of the enzyme was generated using the structure of Aspartate carbamoyltransferase of Pyrococcus abyssi (PDB ID: 1ML4) as template by comparative modeling and validated by various structural quality validation tools. The model was stable during the simulation with the equilibrium root-mean-square standard deviation value of ~1 A. Results from structure assessment tools indicated the reasonably good quality of model. Several inhibitor molecules were docked in the active site of the modeled protein for determining the binding affinity of these molecules toward the protein. Out of various inhibitors used in the study, 3-(4-Hydroxy-phenyl)-2-(2-phosphono-acetylamino)-propionic acid showed highest binding affinity towards ACT. This study provides new insights towards understanding the 3-D Pf ACT structure and binding affinity of selected inhibitor compounds and also paves a way for designing novel anti-malarials.

Aspartate carbamoyltransferase of Plasmodium falciparum as a potential drug target for designing anti-malarial chemotherapeutic agents

Diabetes is a metabolic disorder that has emerged recently as a major cause of global concern. Regulation of the blood glucose concentration is essential to maintain the homeostasis. GLUT2, a carrier protein, plays an important role in transporting sugar molecules across the membrane. To understand the function of this carrier molecule, knowledge of its three-dimensional structure is of paramount importance. Homology modeling approach was adopted to decipher the three-dimensional structure and features of human GLUT2. Ninety-eight percent residues of the modeled structure lie in the allowed region of the Ramachandran plot and a RMSD of 0.86 A with the template molecule confirms the reliability of the modeled structure. Comparative transmembrane helix prediction from primary sequence as well as analysis of model revealed presence of 12 helices, which is in agreement with the available literature. Molecular mechanical calculations and docking analysis were performed for the selected 33 compounds. Results showed Glipizide as the best interacting ligand based on the fitness values scored from the binding affinity and minimized energy of the docked complex. These results will aid in efficient designing of inhibitor molecules to curb diabetes.

G. V. Padmavati

Papers

Probing the structure of human glucose transporter 2 and analysis of protein ligand interactions