The Experts below are selected from a list of 23052 Experts worldwide ranked by ideXlab platform
Benoit Roux - One of the best experts on this subject based on the ideXlab platform.
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Computing Relative Binding Affinity of Ligands to Receptor: An Effective Hybrid Single-Dual-Topology Free-Energy Perturbation Approach in NAMD
Journal of chemical information and modeling, 2019Co-Authors: Wei Jiang, Christophe Chipot, Benoit RouxAbstract:An effective hybrid single-dual-topology protocol is designed for the calculation of relative binding affinities of small ligands to a receptor. The protocol was developed as an extension of the NAMD molecular dynamics program, which exclusively supports a dual-topology framework for relative alchemical free-energy perturbation (FEP) calculations. In this protocol, the alchemical end states are represented as two separate molecules sharing a common substructure identified through maximum structural mapping. Within the substructure, an atom-to-atom correspondence is established, and each pair of corresponding atoms is holonomically constrained to share identical coordinates at all time throughout the simulation. The forces are projected and combined at each step for propagation. Following this formulation, a set of illustrative calculations of reliable experiment/simulation data, including relative solvation free energies of small molecules and relative binding affinities of drug compounds to proteins, are presented. To enhance sampling of the dual-topology region, the FEP calculations were carried out within a replica-exchange MD scheme supported by the multiple-copy algorithm module of NAMD, with periodically attempted swapping of the Thermodynamic Coupling parameter λ between neighboring states. The results are consistent with experiments and benchmarks reported in the literature, lending support to the validity of the current protocol. In summary, this hybrid single-dual-topology approach combines the conceptual simplicity of the dual-topology paradigm with the advantageous sampling efficiency of the single-topology approach, making it an ideal strategy for high-throughput in silico drug design.
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reduced free energy perturbation hamiltonian replica exchange molecular dynamics method with unbiased alchemical Thermodynamic axis
Journal of Physical Chemistry B, 2018Co-Authors: Wei Jiang, Jonathan Thirman, Sunhwan Jo, Benoit RouxAbstract:Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical Thermodynamic Coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W.; Roux, B., J. Chem. Theory Comput. 2010, 6 (9), 2559–2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical Thermodynamic Coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework ...
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free energy perturbation hamiltonian replica exchange molecular dynamics fep h remd for absolute ligand binding free energy calculations
Journal of Chemical Theory and Computation, 2010Co-Authors: Wei Jiang, Benoit RouxAbstract:Free Energy Perturbation with Replica Exchange Molecular Dynamics (FEP/REMD) offers a powerful strategy to improve the convergence of free energy computations. In particular, it has been shown previously that a FEP/REMD scheme allowing random moves within an extended replica ensemble of Thermodynamic Coupling parameters “λ” can improve the statistical convergence in calculations of absolute binding free energy of ligands to proteins [J. Chem. Theory Comput. 2009, 5, 2583]. In the present study, FEP/REMD is extended and combined with an accelerated MD simulations method based on Hamiltonian replica-exchange MD (H-REMD) to overcome the additional problems arising from the existence of kinetically trapped conformations within the protein receptor. In the combined strategy, each system with a given Thermodynamic Coupling factor λ in the extended ensemble is further coupled with a set of replicas evolving on a biased energy surface with boosting potentials used to accelerate the interconversion among different...
Wei Jiang - One of the best experts on this subject based on the ideXlab platform.
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Computing Relative Binding Affinity of Ligands to Receptor: An Effective Hybrid Single-Dual-Topology Free-Energy Perturbation Approach in NAMD
Journal of chemical information and modeling, 2019Co-Authors: Wei Jiang, Christophe Chipot, Benoit RouxAbstract:An effective hybrid single-dual-topology protocol is designed for the calculation of relative binding affinities of small ligands to a receptor. The protocol was developed as an extension of the NAMD molecular dynamics program, which exclusively supports a dual-topology framework for relative alchemical free-energy perturbation (FEP) calculations. In this protocol, the alchemical end states are represented as two separate molecules sharing a common substructure identified through maximum structural mapping. Within the substructure, an atom-to-atom correspondence is established, and each pair of corresponding atoms is holonomically constrained to share identical coordinates at all time throughout the simulation. The forces are projected and combined at each step for propagation. Following this formulation, a set of illustrative calculations of reliable experiment/simulation data, including relative solvation free energies of small molecules and relative binding affinities of drug compounds to proteins, are presented. To enhance sampling of the dual-topology region, the FEP calculations were carried out within a replica-exchange MD scheme supported by the multiple-copy algorithm module of NAMD, with periodically attempted swapping of the Thermodynamic Coupling parameter λ between neighboring states. The results are consistent with experiments and benchmarks reported in the literature, lending support to the validity of the current protocol. In summary, this hybrid single-dual-topology approach combines the conceptual simplicity of the dual-topology paradigm with the advantageous sampling efficiency of the single-topology approach, making it an ideal strategy for high-throughput in silico drug design.
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reduced free energy perturbation hamiltonian replica exchange molecular dynamics method with unbiased alchemical Thermodynamic axis
Journal of Physical Chemistry B, 2018Co-Authors: Wei Jiang, Jonathan Thirman, Sunhwan Jo, Benoit RouxAbstract:Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical Thermodynamic Coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W.; Roux, B., J. Chem. Theory Comput. 2010, 6 (9), 2559–2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical Thermodynamic Coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework ...
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Reduced Free Energy Perturbation/Hamiltonian Replica Exchange Molecular Dynamics Method with Unbiased Alchemical Thermodynamic Axis
2018Co-Authors: Wei Jiang, Jonathan Thirman, Benoît RouxAbstract:Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical Thermodynamic Coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W.; Roux, B., J. Chem. Theory Comput. 2010, 6 (9), 2559–2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical Thermodynamic Coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework of NAMD enables a user to design customized replica-exchange patterns through Tcl scripting in the context of a highly parallelized simulation program without touching the source code. Two Hamiltonian tempering boosting scheme were examined with the new algorithm: a first one based on potential energy rescaling of a preidentified “solute” and a second one via the introduction of flattening torsional free-energy barriers. As two illustrative examples with reliable experiment data, the absolute binding free energies of p-xylene and n-butylbenzene to the nonpolar cavity of the L99A mutant of T4 lysozyme were calculated. The tests demonstrate that the new protocol efficiently enhances the sampling of torsional motions for backbone and side chains around the binding pocket and accelerates the convergence of the free-energy computations
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free energy perturbation hamiltonian replica exchange molecular dynamics fep h remd for absolute ligand binding free energy calculations
Journal of Chemical Theory and Computation, 2010Co-Authors: Wei Jiang, Benoit RouxAbstract:Free Energy Perturbation with Replica Exchange Molecular Dynamics (FEP/REMD) offers a powerful strategy to improve the convergence of free energy computations. In particular, it has been shown previously that a FEP/REMD scheme allowing random moves within an extended replica ensemble of Thermodynamic Coupling parameters “λ” can improve the statistical convergence in calculations of absolute binding free energy of ligands to proteins [J. Chem. Theory Comput. 2009, 5, 2583]. In the present study, FEP/REMD is extended and combined with an accelerated MD simulations method based on Hamiltonian replica-exchange MD (H-REMD) to overcome the additional problems arising from the existence of kinetically trapped conformations within the protein receptor. In the combined strategy, each system with a given Thermodynamic Coupling factor λ in the extended ensemble is further coupled with a set of replicas evolving on a biased energy surface with boosting potentials used to accelerate the interconversion among different...
Yongzhen Wang - One of the best experts on this subject based on the ideXlab platform.
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Thermodynamic optimization of rankine cycle using co2 based binary zeotropic mixture for ocean thermal energy conversion
Applied Thermal Engineering, 2020Co-Authors: Chengyu Li, Yongzhen WangAbstract:Abstract This work provides an exploration on improving the performance of a closed ocean thermal energy conversion (OTEC) system. In order to approach the Lorenz cycle and obtain better thermal matching, a Rankine cycle using CO2-based binary zeotropic mixtures is considered. Six organic working fluids, including R134a, R152a, R161, R1234yf, R1234ze(E) and R32, are selected to be additives for binary mixtures, in addition, various concentrations of CO2 are investigated in order to obtain varying temperature glide. Besides, pure working fluids, including NH3 and CO2, are also comparatively investigated with the mixtures. The specific net power output and thermal efficiency are used to evaluate OTEC Thermodynamic performance, and the ratio of net power output to total heat transfer area is adopted for a preliminary economic analysis. Different effects on cycle performance are analyzed. Finally, an overall optimization to maximize the system thermal efficiency and specific work are carried out, respectively. The simulation is based on a designed Matlab program. The results indicate that CO2-based binary zeotropic mixtures could improve Thermodynamic Coupling of cycle and external seawater, achieving a deeper heat utilization of warm/cold seawater than that of pure working fluid. The performance of Rankine cycle is affected by the mixture composition, and composition at which mixture has evaporating temperature glide of 7-8 °C is recommended. The binary mixtures produce larger specific power output than pure working fluids, and CO2/R32 (0.76/0.24 wt%) produces the maximum value of 0.696 kJ/kg, nearly 38% higher than that of pure NH3. Although the mixtures are inferior to NH3 according to preliminary economic analysis. The Thermodynamic findings still prove that Rankine cycle with CO2-based binary mixture is a promising alternative for OTEC system.
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Thermodynamic optimization of rankine cycle using co2 based binary zeotropic mixture for ocean thermal energy conversion
Applied Thermal Engineering, 2020Co-Authors: Yongzhen WangAbstract:Abstract This work provides an exploration on improving the performance of a closed ocean thermal energy conversion (OTEC) system. In order to approach the Lorenz cycle and obtain better thermal matching, a Rankine cycle using CO2-based binary zeotropic mixtures is considered. Six organic working fluids, including R134a, R152a, R161, R1234yf, R1234ze(E) and R32, are selected to be additives for binary mixtures, in addition, various concentrations of CO2 are investigated in order to obtain varying temperature glide. Besides, pure working fluids, including NH3 and CO2, are also comparatively investigated with the mixtures. The specific net power output and thermal efficiency are used to evaluate OTEC Thermodynamic performance, and the ratio of net power output to total heat transfer area is adopted for a preliminary economic analysis. Different effects on cycle performance are analyzed. Finally, an overall optimization to maximize the system thermal efficiency and specific work are carried out, respectively. The simulation is based on a designed Matlab program. The results indicate that CO2-based binary zeotropic mixtures could improve Thermodynamic Coupling of cycle and external seawater, achieving a deeper heat utilization of warm/cold seawater than that of pure working fluid. The performance of Rankine cycle is affected by the mixture composition, and composition at which mixture has evaporating temperature glide of 7-8 °C is recommended. The binary mixtures produce larger specific power output than pure working fluids, and CO2/R32 (0.76/0.24 wt%) produces the maximum value of 0.696 kJ/kg, nearly 38% higher than that of pure NH3. Although the mixtures are inferior to NH3 according to preliminary economic analysis. The Thermodynamic findings still prove that Rankine cycle with CO2-based binary mixture is a promising alternative for OTEC system.
Jonathan Thirman - One of the best experts on this subject based on the ideXlab platform.
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reduced free energy perturbation hamiltonian replica exchange molecular dynamics method with unbiased alchemical Thermodynamic axis
Journal of Physical Chemistry B, 2018Co-Authors: Wei Jiang, Jonathan Thirman, Sunhwan Jo, Benoit RouxAbstract:Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical Thermodynamic Coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W.; Roux, B., J. Chem. Theory Comput. 2010, 6 (9), 2559–2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical Thermodynamic Coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework ...
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Reduced Free Energy Perturbation/Hamiltonian Replica Exchange Molecular Dynamics Method with Unbiased Alchemical Thermodynamic Axis
2018Co-Authors: Wei Jiang, Jonathan Thirman, Benoît RouxAbstract:Replica-exchange molecular dynamics (REMD) has been proven to efficiently improve the convergence of free-energy perturbation (FEP) calculations involving considerable reorganization of their surrounding. We previously introduced the FEP/(λ,H)-REMD algorithm for ligand binding, in which replicas along the alchemical Thermodynamic Coupling axis λ were expanded as a series of Hamiltonian boosted replicas along a second axis to form a two-dimensional replica-exchange exchange map [Jiang, W.; Roux, B., J. Chem. Theory Comput. 2010, 6 (9), 2559–2565]. Aiming to achieve a similar performance at a lower computational cost, we propose here a modified version of this algorithm in which only the end-states along the alchemical axis are augmented by boosted replicas. The reduced FEP/(λ,H)-REMD method with one-dimensional unbiased alchemical Thermodynamic Coupling axis λ is implemented on the basis of generic multiple copy algorithm (MCA) module of the biomolecular simulation program NAMD. The flexible MCA framework of NAMD enables a user to design customized replica-exchange patterns through Tcl scripting in the context of a highly parallelized simulation program without touching the source code. Two Hamiltonian tempering boosting scheme were examined with the new algorithm: a first one based on potential energy rescaling of a preidentified “solute” and a second one via the introduction of flattening torsional free-energy barriers. As two illustrative examples with reliable experiment data, the absolute binding free energies of p-xylene and n-butylbenzene to the nonpolar cavity of the L99A mutant of T4 lysozyme were calculated. The tests demonstrate that the new protocol efficiently enhances the sampling of torsional motions for backbone and side chains around the binding pocket and accelerates the convergence of the free-energy computations
Chengyu Li - One of the best experts on this subject based on the ideXlab platform.
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Thermodynamic optimization of rankine cycle using co2 based binary zeotropic mixture for ocean thermal energy conversion
Applied Thermal Engineering, 2020Co-Authors: Chengyu Li, Yongzhen WangAbstract:Abstract This work provides an exploration on improving the performance of a closed ocean thermal energy conversion (OTEC) system. In order to approach the Lorenz cycle and obtain better thermal matching, a Rankine cycle using CO2-based binary zeotropic mixtures is considered. Six organic working fluids, including R134a, R152a, R161, R1234yf, R1234ze(E) and R32, are selected to be additives for binary mixtures, in addition, various concentrations of CO2 are investigated in order to obtain varying temperature glide. Besides, pure working fluids, including NH3 and CO2, are also comparatively investigated with the mixtures. The specific net power output and thermal efficiency are used to evaluate OTEC Thermodynamic performance, and the ratio of net power output to total heat transfer area is adopted for a preliminary economic analysis. Different effects on cycle performance are analyzed. Finally, an overall optimization to maximize the system thermal efficiency and specific work are carried out, respectively. The simulation is based on a designed Matlab program. The results indicate that CO2-based binary zeotropic mixtures could improve Thermodynamic Coupling of cycle and external seawater, achieving a deeper heat utilization of warm/cold seawater than that of pure working fluid. The performance of Rankine cycle is affected by the mixture composition, and composition at which mixture has evaporating temperature glide of 7-8 °C is recommended. The binary mixtures produce larger specific power output than pure working fluids, and CO2/R32 (0.76/0.24 wt%) produces the maximum value of 0.696 kJ/kg, nearly 38% higher than that of pure NH3. Although the mixtures are inferior to NH3 according to preliminary economic analysis. The Thermodynamic findings still prove that Rankine cycle with CO2-based binary mixture is a promising alternative for OTEC system.
