scholarly journals Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations

2012 ◽  
Vol 13 (2) ◽  
pp. 2176-2195 ◽  
Author(s):  
Jianzhong Chen ◽  
Dinglin Zhang ◽  
Yuxin Zhang ◽  
Guohui Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Peptide Inhibitors ◽  
Computational Studies ◽  
Binding Modes ◽  
Dynamics Simulations

scholarly journals Molecular Dynamics Simulations of Peptide Inhibitors Complexed WithTrypanosoma cruziTrypanothione Reductase

2012 ◽  
Vol 80 (4) ◽  
pp. 561-571 ◽  
Author(s):  
Samuel Silva Da Rocha Pita ◽  
Paulo Ricardo Batista ◽  
Magaly Girão Albuquerque ◽  
Pedro Geraldo Pascutti
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Peptide Inhibitors ◽  
Dynamics Simulations

scholarly journals Oxidation-induced destabilization of the fibrinogen αC-domain dimer investigated by molecular dynamics simulations

2018 ◽  
Author(s):  
Eric N. Pederson ◽  
Gianluca Interlandi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Blood Clot ◽  
Long Strings ◽  
Methionine Sulfoxide ◽  
Binding Modes ◽  
Vein Thrombosis ◽  
Fibrin Matrix ◽  
Dynamics Simulations ◽  
Deep Vein

AbstractUpon activation, fibrinogen is converted to insoluble fibrin, which assembles into long strings called protofibrils. These aggregate laterally to form a fibrin matrix that stabilizes a blood clot. Lateral aggregation of protofibrils is mediated by the αC domain, a partially structured fragment located in a disordered region of fibrinogen. Polymerization of αC domains links multiple fibrin molecules with each other enabling the formation of thick fibrin fibers and a fibrin matrix that is stable but can also be digested by enzymes. How-ever, oxidizing agents produced during the inflammatory response have been shown to cause thinner fibrin fibers resulting in denser clots, which are harder to proteolyze and pose the risk of deep vein thrombosis and lung embolism. It has been postulated that oxidation of Met476 located within the αC domain hinders its ability to polymerize disrupting the lateral aggregation of protofibrils and leading to the observed thinner fibers. How αC domains assemble into polymers is still unclear and yet this knowledge would shed light on the mechanism through which oxidation weakens the lateral aggregation of protofibrils. This study used temperature replica exchange molecular dynamics simulations to investigate the αC-domain dimer and how this is affected by oxidation of Met476. The results suggest that multiple binding modes between two alphaC domains can occur and that oxidation decreases the likelihood of dimer formation. Furthermore, the side chain of Met476 acts as a docking spot between αC domains and this function is abrogated by its conversion to methionine sulfoxide.

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