Identification of Novel Potential Anti-Diabetic Candidates targeting Human Pancreatic ɑ-Amylase and Human ɑ-Glycosidase: An Exhaustive Structure-based Screening

2021 ◽  
Author(s):  
Deepika Maliwal ◽  
Raghuvir R. S. Pissurlenkar ◽  
Vikas Telvekar
Keyword(s):  
Medical Condition ◽  
Computational Study ◽  
Well Being ◽  
Vital Role ◽  
The Body ◽  
Free Energies ◽  
Protein Ligand Interactions ◽  
Depth Analysis ◽  
Ligand Interactions ◽  
Binding Free Energies

Diabetes is a major health issue that half a billion people affected worldwide. It is a serious, long-term medical condition majorly impacting the lives and well-being of individuals, families, and societies at large. It is amongst the top 10 diseases responsible for the death amongst adults with an expected rise to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. The carbohydrates absorbed into the body are hydrolyzed by pancreatic α-amylase and other enzymes, human α-glucosidase. The α-amylase and α-glucosidase are validated therapeutic targets in the treatment of Type II diabetes (T2DM) as they play a vital role in modulating the blood glucose post meal. Herein, we report novel and diverse molecules as potential candidates, with predicted affinity for α-amylase and α-glucosidase. These molecules have been identified via hierarchical multistep docking of small molecules database with the estimated binding free energies. A Glide XP Score cutoff −8.00 kcal/mol was implemented to filter out non potential molecules. Four molecules viz. amb22034702, amb18105639, amb17153304, and amb9760832 have been identified after an exhaustive computational study involving, evaluation of binding interactions and assessment of the pharmacokinetics and toxicity profiles. The in-depth analysis of protein– ligand interactions was performed using a 100ns molecular dynamics (MD) simulation to establish the dynamic stability. Furthermore MM-GBSA based binding free energies were computed for 1000 trajectory snapshots to ascertain the strong binding affinity of these molecules for α-amylase and αglucosidase. The identified molecules can be considered as promising candidates for further drug development through necessary experimental assessments.

A Survey for Predicting ATP Binding Residues of Proteins Using Machine Learning Methods

2021 ◽  
Vol 28 ◽  
Author(s):  
Yu-He Yang ◽  
Jia-Shu Wang ◽  
Shi-Shi Yuan ◽  
Meng-Lu Liu ◽  
Wei Su ◽  
...  
Keyword(s):  
Machine Learning ◽  
Protein Function ◽  
Vital Role ◽  
Atp Binding ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Protein Ligand Interactions ◽  
Protein Functions ◽  
Ligand Interactions ◽  
Binding Residues

: Protein-ligand interactions are necessary for majority protein functions. Adenosine-5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is cost-ineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

scholarly journals RELATIONSHIP BETWEEN POOR DIGESTION AND DISEASE IN PERSPECTIVE OF GRECOARAB MEDICINE

2020 ◽  
pp. 46-47
Author(s):  
Tasfiya Hakeem Ansari ◽  
Mohd. Zulkifle
Keyword(s):  
Skin Diseases ◽  
Well Being ◽  
Relevant Information ◽  
Vital Role ◽  
The Body ◽  
Classical Literature ◽  
Broad Term ◽  
Extensive Stage ◽  
Mental Well Being ◽  
The Relationship

Ingested food undergoes extensive stage-wise processing inside the body so that it can provide nourishment to the tissues. This stage-wise processing of food in Greco-Arab medicine is known as digestion. Innate heat plays a vital role in digestion. In Greco-Arab medicine, digestion is a broad term that includes digestion as well as the metabolism of food. Physicians like Galen, Rhazes and Avicenna, etc. believed that good digestion plays a key role in corporal and mental well being. In the classical literature of Greco-Arab medicine various diseases are described that are caused by poor digestion. Several skin diseases like acne as well as mental diseases like depression etc. are related to poor digestion. This relationship between poor digestion and disease is attributed to the production of morbid matter. Relevant literary material is collected from the classical literature of Greco-Arab medicine. Present work is an attempt to analyze and systematize the relevant information regarding the relationship between poor digestion and disease.

A Computational Study on Rotor and Fuselage Configuration Effect on Rotorcraft Brownout

2021 ◽  
Author(s):  
Sayan Ghosh ◽  
R. Ganesh Rajagopalan
Keyword(s):  
Significant Role ◽  
Computational Study ◽  
Dust Cloud ◽  
Vital Role ◽  
The Body ◽  
Dust Particles ◽  
Computationally Efficient ◽  
Dust Clouds ◽  
Simpler Algorithm ◽  
Rotorcraft Brownout

Rotorcraft brownout is an in-flight visibility restriction caused by clouds of sand and dust particles during landing, takeoff, and near-ground flight operations in arid desert terrain. This complex phenomenon is caused by the entrainment of dust, sand, and ground particles by rotor downwash and is compounded by fuselage geometry and its orientation with respect to the ground. Highly unsteady wind velocities are common in near-ground operations and play a significant role in the particulate cloud’s behavior that creates the brownout condition. Experiments and flight tests to understand brownout are challenging, expensive, and risky. Alternatively, computational fluid dynamics (CFD) has been used extensively over the past few decades to study rotorcraft aerodynamics. However, there are additional computational challenges associated with modeling the dust particle transport in a brownout. In this work, a computationally efficient Eulerian-based framework has been developed to model rotorcraft brownout. The flowfield is modeled by Reynolds averaged Navier–Stokes (RANS) equation and is solved using the SIMPLER algorithm. Turbulence properties are modeled using Realizable k – ε equations, while the rotor is modeled as a momentum source to focus on the global flowfield rather than the flow near the rotors. The Eulerian approach for both the flowfield and the dust transport allows computationally efficient and rapid analysis, taking an order of few hours in a single CPU to a fraction of an hour using GPU-based computation. In this work, results from two sets of experiments are presented. At first, a study on the fuselage’s effect on brownout with respect to height for a single-rotor configuration in hover is demonstrated. Next, a study on the brownout characteristics of three rotor–fuselage configurations in hover, namely single-rotor, tandem-rotor, and quad-rotor, is presented. It has been observed that the ground friction velocity profile and flowfield vorticity around the rotorcraft play a significant role in dust cloud behavior. Additionally, the body forces and interference due to the fuselage plays a vital role in the formation of brownout dust clouds. The experiments showed that the quad-rotor is worst affected in terms of size and height of the dust clouds. However, the tandem-rotor has been found to be worst in the terms of average dust density.

Computational Modeling of Solvent Effects on Protein-Ligand Interactions Using Fully Polarizable Continuum Model and Rational Drug Design

2013 ◽  
Vol 13 (1) ◽  
pp. 31-60 ◽  
Author(s):  
Fang Zheng ◽  
Chang-Guo Zhan
Keyword(s):  
Drug Design ◽  
Computational Modeling ◽  
Molecular Species ◽  
Solvent Effects ◽  
Polarizable Continuum Model ◽  
Rational Drug Design ◽  
Free Energies ◽  
Protein Ligand Interactions ◽  
Rational Drug ◽  
Ligand Interactions

AbstractThis is a brief review of the computational modeling of protein-ligand interactions using a recently developed fully polarizable continuum model (FPCM) and rational drug design. Computational modeling has become a powerful tool in understanding detailed protein-ligand interactions at molecular level and in rational drug design. To study the binding of a protein with multiple molecular species of a ligand, one must accurately determine both the relative free energies of all of the molecular species in solution and the corresponding microscopic binding free energies for all of the molecular species binding with the protein. In this paper, we aim to provide a brief overview of the recent development in computational modeling of the solvent effects on the detailed protein-ligand interactions involving multiple molecular species of a ligand related to rational drug design. In particular, we first briefly discuss the main challenges in computational modeling of the detailed protein-ligand interactions involving the multiple molecular species and then focus on the FPCM model and its applications. The FPCM method allows accurate determination of the solvent effects in the first-principles quantum mechanism (QM) calculations on molecules in solution. The combined use of the FPCM-based QM calculations and other computational modeling and simulations enables us to accurately account for a protein binding with multiple molecular species of a ligand in solution. Based on the computational modeling of the detailed protein-ligand interactions, possible new drugs may be designed rationally as either small-molecule ligands of the protein or engineered proteins that bind/metabolize the ligand. The computational drug design has successfully led to discovery and development of promising drugs.

scholarly journals Knowledge, Awareness, Prevalence and Frequency of Daily Physical Activity and Its Association with Stroke in Young Adult Population

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 507-513
Author(s):  
Sai Sanjith A ◽  
Karthik Ganesh Mohanraj
Keyword(s):  
Physical Activity ◽  
Medical Condition ◽  
Human Life ◽  
Adult Population ◽  
Well Being ◽  
Health Condition ◽  
The Body ◽  
Daily Physical Activity ◽  
Medical Emergency ◽  
The Brain

Stroke is a medical condition affecting the brain. It occurs when the blood supply to the brain or part of the brain is stopped or reduced, preventing the brain cells from getting oxygen. As the neurons are the most sensitive cells in the body, they tend to die after cessation of oxygen supply for a very few minutes. Several remedial measures are available for this medical emergency at the time of stroke and even after that. It is believed that the stroke recurs after time and thus preparatory and cautionary steps to be carried out for survival. Among that daily physical activity seems to have a greater positive approach towards stroke survivors. In general, physical activity is an essential part of human life which many people neglect. But it has an underlying significance for human life and healthy well-being. It maintains the body's health condition free of certain diseases too. Thus, this study attempts to analyze the awareness and to knowledge the people about the association between stroke and daily physical activity.

scholarly journals Simulating the directional translocation of a substrate by the AAA+ motor in the 26S proteasome

2021 ◽  
Vol 118 (23) ◽  
pp. e2104245118
Author(s):  
Arjun Saha ◽  
Arieh Warshel
Keyword(s):  
Electrostatic Interactions ◽  
Atp Hydrolysis ◽  
Computational Study ◽  
26S Proteasome ◽  
Coarse Grained ◽  
Free Energies ◽  
Ongoing Research ◽  
Lysine Residues ◽  
Coarse Grained Simulations ◽  
Binding Free Energies

This work explored the molecular origin of substrate translocation by the AAA+ motor of the 26S proteasome. This exploration was performed by combining different simulation approaches including calculations of binding free energies, coarse-grained simulations, and considerations of the ATP hydrolysis energy. The simulations were used to construct the free energy landscape for the translocation process. This included the evaluation of the conformational barriers in different translocation steps. Our simulation reveals that the substrate translocation by the AAA+ motor is guided in part by electrostatic interactions. We also validated the experimental observation that bulkier residues in pore loop 1 are responsible for substrate translocation. However, our calculation also reveals that the lysine residues prior to the bulkier residues (conserved along pore loop 1) are also important for the translocation process. We believe that this computational study can help in guiding the ongoing research of the proteasome.

scholarly journals A CRITICAL REVIEW OF ABHYANGA WITH SPECIAL REFERENCE TO ITS CONTEMPORARY RELEVANCE

2021 ◽  
Vol 10 (2) ◽  
pp. 32-37
Author(s):  
Archana Raman Belge ◽  
Raman Shankar Belge
Keyword(s):  
Quality Of Life ◽  
Special Reference ◽  
Critical Review ◽  
Blood Circulation ◽  
Well Being ◽  
Vital Role ◽  
The Body ◽  
Whole Body ◽  
Critical Study

Abhayanga is one of the foremost massage maneuvers mentioned in the Ayurvedic texts like Brihattrayi and Laghutrayi. It is the oldest technique for healing, preventing diseases and promoting health. It has been included in the Dinacharya and also as the treatment measure for a variety of diseases. It is also a part of the pre-therapeutic procedures of Panchakarma. Abhyanga improves blood circulation (arterial as well as venous), lymphatic flow and thus offers nourishment to the body cells. It not only de-stresses the whole body but also strengthens the nervous system, improves blood circulation, removes toxins and improves the overall well-being of the person. Besides offering an immuno-modulatory action, it improves the quality of life thus benefitting the persons of all the ages. The ancient Ayurvedic literature as well as modern references was referred to have a critical study of the classification of massage; to compare between Abhyanga and Massage; to study the mode of action according to Ayurvedic and modern view. This being the Bahiparimarjana Chikitsa plays a vital role in improving the quality of life, thus fulfilling the basic motto of Ayurveda. Modern studies have proven that, Abhyanga has potential psychogenic and physiologic benefits. It can certainly be said that Abhyanga, “Adds life to years” rather than “Years to life” and thus bears a strong contemporary relevance. This review article is meant to have a critical review of Abhyanga with special reference to its contemporary relevance.

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