Computational study on the unbinding pathways of B-RAF inhibitors and its implication for the difference of residence time: insight from random acceleration and steered molecular dynamics simulations

2016 ◽  
Vol 18 (7) ◽  
pp. 5622-5629 ◽  
Author(s):  
Yuzhen Niu ◽  
Shuyan Li ◽  
Dabo Pan ◽  
Huanxiang Liu ◽  
Xiaojun Yao
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Residence Time ◽  
Computational Study ◽  
Steered Molecular Dynamics ◽  
The Difference ◽  
Random Acceleration ◽  
Dynamics Simulations

Random acceleration and steered molecular dynamics simulations reveal the unbinding pathway of B-RAF inhibitors and the difference in the residence time.

scholarly journals Computational Study for the Unbinding Routes of β-N-Acetyl-d-Hexosaminidase Inhibitor: Insight from Steered Molecular Dynamics Simulations

2019 ◽  
Vol 20 (6) ◽  
pp. 1516
Author(s):  
Song Hu ◽  
Xiao Zhao ◽  
Li Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Computational Study ◽  
Steered Molecular Dynamics ◽  
Amino Acid Residues ◽  
Ostrinia Furnacalis ◽  
Pharmacodynamic Effect ◽  
Dynamics Simulations ◽  
Potential Of Mean Forces

β-N-Acetyl-d-hexosaminidase from Ostrinia furnacalis (OfHex1) is a new target for the design of insecticides. Although some of its inhibitors have been found, there is still no commercial drug available at present. The residence time of the ligand may be important for its pharmacodynamic effect. However, the unbinding routes of ligands from OfHex1 still remain largely unexplored. In the present study, we first simulated the six dissociation routes of N,N,N-trimethyl-d-glucosamine-chitotriomycin (TMG-chitotriomycin, a highly selective inhibitor of OfHex1) from the active pocket of OfHex1 by steered molecular dynamics simulations. By comparing the potential of mean forces (PMFs) of six routes, Route 1 was considered as the most possible route with the lowest energy barrier. Furthermore, the structures of six different states for Route 1 were snapshotted, and the key amino acid residues affecting the dissociated time were analyzed in the unbinding pathway. Moreover, we also analyzed the “open–close” mechanism of Glu368 and Trp448 and found that their conformational changes directly affected the dissociation of TMG-chitotriomycin. Our findings would be helpful to understanding and identifying novel inhibitors against OfHex1 from virtual screening or lead-optimization.

Exploring the different ligand escape pathways in acylaminoacyl peptidase by random acceleration and steered molecular dynamics simulations

RSC Advances ◽  
2016 ◽  
Vol 6 (13) ◽  
pp. 10987-10996 ◽  
Author(s):  
Hanyong Jin ◽  
Jingxuan Zhu ◽  
Yang Dong ◽  
Weiwei Han
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Steered Molecular Dynamics ◽  
Prolyl Oligopeptidase ◽  
Acylaminoacyl Peptidase ◽  
Random Acceleration ◽  
Dynamics Simulations

Acylaminoacyl peptidase (APH, EC 3.4.19.1) is a novel class of serine-type protease belonging to the prolyl oligopeptidase (POP) family.

Liquid dibromomethane under pressure: a computational study

2021 ◽  
Vol 23 (4) ◽  
pp. 2964-2971
Author(s):  
Bernadeta Jasiok ◽  
Mirosław Chorążewski ◽  
Eugene B. Postnikov ◽  
Claude Millot
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Thermophysical Properties ◽  
Computational Study ◽  
Thermal Expansivity ◽  
Dynamics Simulations ◽  
Isobaric Thermal Expansivity

Thermophysical properties of liquid dibromomethane are investigated by molecular dynamics simulations between 268 and 328 K at pressures up to 3000 bar. Notably, the isotherms of the isobaric thermal expansivity cross around 800 bar.

The Computational Study of Microchannel Thickness Effects on H2O/CuO Nanofluid Flow with Molecular Dynamics Simulations

2021 ◽  
pp. 118240
Author(s):  
Yanpeng Shang ◽  
Reza Balali Dehkordi ◽  
Supat Chupradit ◽  
Davood Toghraie ◽  
Andrei Sevbitov ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Computational Study ◽  
Nanofluid Flow ◽  
Dynamics Simulations

scholarly journals Molecular dynamics simulations of mechanical failure in polymorphic arrangements of amyloid fibrils containing structural defects

2013 ◽  
Vol 4 ◽  
pp. 429-440 ◽  
Author(s):  
Hlengisizwe Ndlovu ◽  
Alison E Ashcroft ◽  
Sheena E Radford ◽  
Sarah A Harris
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Steered Molecular Dynamics ◽  
Mechanical Failure ◽  
Structural Defects ◽  
Dynamics Simulations

We examine how the different steric packing arrangements found in amyloid fibril polymorphs can modulate their mechanical properties using steered molecular dynamics simulations. Our calculations demonstrate that for fibrils containing structural defects, their ability to resist force in a particular direction can be dominated by both the number and molecular details of the defects that are present. The simulations thereby suggest a hierarchy of factors that govern the mechanical resilience of fibrils, and illustrate the general principles that must be considered when quantifying the mechanical properties of amyloid fibres containing defects.

scholarly journals Molecular Insights into Cage Occupancy of Hydrogen Hydrate: A Computational Study

Processes ◽  
2019 ◽  
Vol 7 (10) ◽  
pp. 699 ◽  
Author(s):  
Ma ◽  
Zhong ◽  
Liu ◽  
Zhong ◽  
Yan ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Storage ◽  
Molecular Dynamics Simulations ◽  
Density Functional ◽  
Storage Capacity ◽  
Computational Study ◽  
Density Functional Theory Calculations ◽  
Hydrogen Storage Capacity ◽  
Large Cage ◽  
Dynamics Simulations

Density functional theory calculations and molecular dynamics simulations were performed to investigate the hydrogen storage capacity in the sII hydrate. Calculation results show that the optimum hydrogen storage capacity is ~5.6 wt%, with the double occupancy in the small cage and quintuple occupancy in the large cage. Molecular dynamics simulations indicate that these multiple occupied hydrogen hydrates can occur at mild conditions, and their stability will be further enhanced by increasing the pressure or decreasing the temperature. Our work highlights that the hydrate is a promising material for storing hydrogen.

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