scholarly journals Calculation of protein-protein binding free energies using umbrella sampling with dual resolution water models

2020 ◽  
Author(s):  
Jagdish Suresh Patel
Keyword(s):  
Protein Binding ◽  
Umbrella Sampling ◽  
Free Energies ◽  
Water Models ◽  
Binding Free Energies

scholarly journals Poisson-Boltzmann Calculations of Nonspecific Salt Effects on Protein-Protein Binding Free Energies

2007 ◽  
Vol 92 (6) ◽  
pp. 1891-1899 ◽  
Author(s):  
Claudia Bertonati ◽  
Barry Honig ◽  
Emil Alexov
Keyword(s):  
Protein Binding ◽  
Free Energies ◽  
Salt Effects ◽  
Poisson Boltzmann ◽  
Binding Free Energies

scholarly journals A replica exchange umbrella sampling (REUS) approach to predict host–guest binding free energies in SAMPL8 challenge

2021 ◽  
Author(s):  
Mahdi Ghorbani ◽  
Phillip S. Hudson ◽  
Michael R. Jones ◽  
Félix Aviat ◽  
Rubén Meana-Pañeda ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Umbrella Sampling ◽  
Free Energy Calculations ◽  
Replica Exchange ◽  
Free Energies ◽  
Guest Binding ◽  
Binding Free Energy Calculations ◽  
Force Field Parameters ◽  
Binding Free Energies

AbstractIn this study, we report binding free energy calculations of various drugs-of-abuse to Cucurbit-[8]-uril as part of the SAMPL8 blind challenge. Force-field parameters were obtained from force-matching with different quantum mechanical levels of theory. The Replica Exchange Umbrella Sampling (REUS) approach was used with a cylindrical restraint to enhance the sampling of host–guest binding. Binding free energy was calculated by pulling the guest molecule from one side of the symmetric and cylindrical host, then into and through the host, and out the other side (bidirectional) as compared to pulling only to the bound pose inside the cylindrical host (unidirectional). The initial results with force-matched MP2 parameter set led to RMSE of 4.68 $${\text{kcal}}/{\text{mol}}$$ kcal / mol from experimental values. However, the follow-up study with CHARMM generalized force field parameters and force-matched PM6-D3H4 parameters resulted in RMSEs from experiment of $$2.65$$ 2.65 and $$1.72 {\text{kcal}}/{\text{mol}}$$ 1.72 kcal / mol , respectively, which demonstrates the potential of REUS for accurate binding free energy calculation given a more suitable description of energetics. Moreover, we compared the free energies for the so called bidirectional and unidirectional free energy approach and found that the binding free energies were highly similar. However, one issue in the bidirectional approach is the asymmetry of profile on the two sides of the host. This is mainly due to the insufficient sampling for these larger systems and can be avoided by longer sampling simulations. Overall REUS shows great promise for binding free energy calculations.

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 Prediction of protein-protein binding free energies

2012 ◽  
Vol 21 (3) ◽  
pp. 396-404 ◽  
Author(s):  
Thom Vreven ◽  
Howook Hwang ◽  
Brian G. Pierce ◽  
Zhiping Weng
Keyword(s):  
Protein Binding ◽  
Free Energies ◽  
Binding Free Energies

Assessing the performance of the MM/PBSA and MM/GBSA methods. 6. Capability to predict protein–protein binding free energies and re-rank binding poses generated by protein–protein docking

2016 ◽  
Vol 18 (32) ◽  
pp. 22129-22139 ◽  
Author(s):  
Fu Chen ◽  
Hui Liu ◽  
Huiyong Sun ◽  
Peichen Pan ◽  
Youyong Li ◽  
...  
Keyword(s):  
Protein Binding ◽  
Protein Interactions ◽  
Protein Docking ◽  
Biological Processes ◽  
Free Energies ◽  
Protein Protein Interactions ◽  
Binding Free Energies

Understanding protein–protein interactions (PPIs) is quite important to elucidate crucial biological processes and even design compounds that interfere with PPIs with pharmaceutical significance.

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