scholarly journals Estimation of a stronger heparin binding locus in fibronectin domain III14 using thermodynamics and molecular dynamics

RSC Advances ◽  
2020 ◽  
Vol 10 (34) ◽  
pp. 20288-20301
Author(s):  
Sakshi Gupta ◽  
Neha Tiwari ◽  
Jyoti Verma ◽  
Mohd Waseem ◽  
Naidu Subbarao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Heparin Binding ◽  
Binding Thermodynamics ◽  
Binding Locus

Binding Thermodynamics of FHIP I and FHIP II with heparin.

scholarly journals Protein-protein interaction-Gaussian accelerated molecular dynamics (PPI-GaMD): Characterization of protein binding thermodynamics and kinetics

2021 ◽  
Author(s):  
Jinan Wang ◽  
Yinglong Miao
Keyword(s):  
Molecular Dynamics ◽  
Potential Energy ◽  
Protein Binding ◽  
Binding Free Energy ◽  
Model System ◽  
Free Energies ◽  
Binding Thermodynamics ◽  
Accelerated Molecular Dynamics ◽  
Thermodynamics And Kinetics ◽  
Binding Free Energies

Protein-protein interactions (PPIs) play key roles in many fundamental biological processes such as cellular signaling and immune responses. However, it has proven challenging to simulate repetitive protein association and dissociation in order to calculate binding free energies and kinetics of PPIs, due to long biological timescales and complex protein dynamics. To address this challenge, we have developed a new computational approach to all-atom simulations of PPIs based on a robust Gaussian accelerated molecular dynamics (GaMD) technique. The method, termed "PPI-GaMD", selectively boosts interaction potential energy between protein partners to facilitate their slow dissociation. Meanwhile, another boost potential is applied to the remaining potential energy of the entire system to effectively model the protein's flexibility and rebinding. PPI-GaMD has been demonstrated on a model system of the ribonuclease barnase interactions with its inhibitor barstar. Six independent 2 µs PPI-GaMD simulations have captured repetitive barstar dissociation and rebinding events, which enable calculations of the protein binding thermodynamics and kinetics simultaneously. The calculated binding free energies and kinetic rate constants agree well with the experimental data. Furthermore, PPI-GaMD simulations have provided mechanistic insights into barstar binding to barnase, which involve long-range electrostatic interactions and multiple binding pathways, being consistent with previous experimental and computational findings of this model system. In summary, PPI-GaMD provides a highly efficient and easy-to-use approach for binding free energy and kinetics calculations of PPIs.

scholarly journals Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics

2020 ◽  
Author(s):  
Yinglong Miao ◽  
Apurba Bhattarai ◽  
Jinan Wang
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Ligand Binding ◽  
Free Energies ◽  
Kinetic Rate ◽  
Binding Thermodynamics ◽  
Accelerated Molecular Dynamics ◽  
Thermodynamics And Kinetics ◽  
Kinetic Rate Constants ◽  
Binding Free Energies

AbstractCalculations of ligand binding free energies and kinetic rates are important for drug design. However, such tasks have proven challenging in computational chemistry and biophysics. To address this challenge, we have developed a new computational method “LiGaMD”, which selectively boosts the ligand non-bonded interaction potential energy based on the Gaussian accelerated molecular dynamics (GaMD) enhanced sampling technique. Another boost potential could be applied to the remaining potential energy of the entire system in a dual-boost algorithm (LiGaMD_Dual) to facilitate ligand binding. LiGaMD has been demonstrated on host-guest and protein-ligand binding model systems. Repetitive guest binding and unbinding in the β-cyclodextrin host were observed in hundreds-of-nanosecond LiGaMD simulations. The calculated binding free energies of guest molecules with sufficient sampling agreed excellently with experimental data (< 1.0 kcal/mol error). In comparison with previous microsecond-timescale conventional molecular dynamics simulations, accelerations of ligand kinetic rate constants in LiGaMD simulations were properly estimated using Kramers’ rate theory. Furthermore, LiGaMD allowed us to capture repetitive dissociation and binding of the benzamidine inhibitor in trypsin within 1 μs simulations. The calculated ligand binding free energy and kinetic rate constants compared well with the experimental data. In summary, LiGaMD provides a promising approach for characterizing ligand binding thermodynamics and kinetics simultaneously, which is expected to facilitate computer-aided drug design.

Hepatoma-Derived Growth Factor (HDGF): A New Heparin-Binding Growth Factor Identified in Leiomyomas and Normal Myometrium

1998 ◽  
Vol 5 (1) ◽  
pp. 180A-180A
Author(s):  
M ISHIKAWA ◽  
S TAKASHIMA ◽  
H NAKAMURA ◽  
M KLAGSBRUN ◽  
R NOWAK
Keyword(s):  
Growth Factor ◽  
Heparin Binding
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