Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1 and GSK-3β: molecular dynamics simulations, binding energy, and network analysis to identify first-in-class dual inhibitors against Alzheimer’s disease

2017 ◽  
Vol 23 (8) ◽  
Author(s):  
Akhil Kumar ◽  
Gaurava Srivastava ◽  
Swati Srivastava ◽  
Seema Verma ◽  
Arvind S. Negi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Molecular Dynamics ◽  
Binding Energy ◽  
Network Analysis ◽  
Molecular Dynamics Simulations ◽  
Dual Inhibitor ◽  
Dual Inhibitors ◽  
Gsk 3Β ◽  
Dynamics Simulations ◽  
Bace 1

scholarly journals Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations

2021 ◽  
Vol 22 (13) ◽  
pp. 6709
Author(s):  
Xiao-Xuan Shi ◽  
Peng-Ye Wang ◽  
Hong Chen ◽  
Ping Xie
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Binding Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Weak Interactions ◽  
Molecular Motor ◽  
Structural Data ◽  
Calculated Binding Energy ◽  
Dynamics Simulations

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot. Furthermore, we found that the large conformational changes of the tubulin have a significant effect on the interaction of the tubulin with the head in the weak-microtubule-binding ADP state. The calculated binding energy of the ADP-bound head to the tubulin with the large conformational changes is only about half that of the tubulin without the conformational changes.

Destabilization of Alzheimer’s Aβ42 protofibrils with acyclovir, carmustine, curcumin, and tetracycline: Insights from molecular dynamics simulations

2021 ◽  
Author(s):  
Ishrat Jahan ◽  
Shahid M Nayeem
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Neurodegenerative Diseases ◽  
Molecular Dynamics Simulations ◽  
Amyloid Β ◽  
Neural Tissue ◽  
Amyloid Β Peptide ◽  
Characteristic Symptom ◽  
Dynamics Simulations

One of the most common dementia among neurodegenerative diseases is Alzheimer’s disease (AD). The characteristic symptom of AD is the deposition and aggregation of amyloid-β-peptide in the neural tissue. A...

Allosteric pathway identification through network analysis: from molecular dynamics simulations to interactive 2D and 3D graphs

2014 ◽  
Vol 169 ◽  
pp. 303-321 ◽  
Author(s):  
Ariane Allain ◽  
Isaure Chauvot de Beauchêne ◽  
Florent Langenfeld ◽  
Yann Guarracino ◽  
Elodie Laine ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Network Analysis ◽  
Molecular Dynamics Simulations ◽  
Large Scale ◽  
Allosteric Regulation ◽  
Local Perturbation ◽  
Modular Network ◽  
Allosteric Coupling ◽  
Dynamics Simulations

Allostery is a universal phenomenon that couples the information induced by a local perturbation (effector) in a protein to spatially distant regulated sites. Such an event can be described in terms of a large scale transmission of information (communication) through a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. To elaborate a rational description of allosteric coupling, we propose an original approach – MOdular NETwork Analysis (MONETA) – based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure. MONETA uses inter-residue cross-correlations and commute times computed from molecular dynamics simulations and a topological description of a protein to build a modular network representation composed of clusters of residues (dynamic segments) linked together by chains of residues (communication pathways). MONETA provides a brand new direct and simple visualization of protein allosteric communication. A GEPHI module implemented in the MONETA package allows the generation of 2D graphs of the communication network. An interactive PyMOL plugin permits drawing of the communication pathways between chosen protein fragments or residues on a 3D representation. MONETA is a powerful tool for on-the-fly display of communication networks in proteins. We applied MONETA for the analysis of communication pathways (i) between the main regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in the phosphorylated and the unphosphorylated forms. The description of the physical support for allosteric coupling by MONETA allowed a comparison of the mechanisms of (a) constitutive activation induced by equivalent mutations in two RTKs and (b) allosteric regulation in the activated and non-activated STAT5 proteins. Our theoretical prediction based on results obtained with MONETA was validated for KIT by in vitro experiments. MONETA is a versatile analytical and visualization tool entirely devoted to the understanding of the functioning/malfunctioning of allosteric regulation in proteins – a crucial basis to guide the discovery of next-generation allosteric drugs.

Sign in / Sign up

Export Citation Format

Share Document