The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Marco Cecchini - One of the best experts on this subject based on the ideXlab platform.
-
Quantum Corrections to the Free Energy Difference between Peptides and Proteins Conformers.
Journal of chemical theory and computation, 2015Co-Authors: Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key in understanding the function of biomolecules and has attracted significant interest in recent years. Most current computational approaches evaluate the difference in Conformational Free Energy in the classical limit based on the common “dogma” that only the lowest-frequency modes make a significant contribution to it, i.e. they assume that quantum mechanical corrections are negligible. Here, I show for three biomolecular systems described in the rigid-rotor, harmonic-oscillator approximation that the zero-point Energy contribution, although small, is not negligible even at room temperature. I find that a quantum correction arises from the intermediate-frequency vibrational modes and that its magnitude is strongly correlated with the number of atoms in the system. A straightforward, though approximate, way to account for this quantum correction in the calculation of Conformational Free-Energy differences by classical molecular dynamics is presented...
-
Accurate calculation of Conformational Free Energy differences in explicit water: the confinement-solvation Free Energy approach.
Journal of Physical Chemistry B, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly...
-
Accurate Calculation of Conformational Free Energy Differences in Explicit Water: The Confinement–Solvation Free Energy Approach B
The Journal of Physical Chemistry, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly converged Free-Energy results were obtained in agreement with equilibrium sampling or literature calculations. These results demonstrate that the CSF method may provide Conformational Free-Energy differences of biomolecules with small statistical errors (below 0.5 kcal/mol) and at a moderate computational cost even with a full representation of the solvent.
-
accurate calculation of Conformational Free Energy differences in explicit water the confinement solvation Free Energy approach b
The Journal of Physical Chemistry, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly converged Free-Energy results were obtained in agreement with equilibrium sampling or literature calculations. These results demonstrate that the CSF method may provide Conformational Free-Energy differences of biomolecules with small statistical errors (below 0.5 kcal/mol) and at a moderate computational cost even with a full representation of the solvent.
-
Conformational Free-Energy Difference of a Miniprotein from Nonequilibrium Simulations
The Journal of Physical Chemistry Letters, 2010Co-Authors: Martin Spichty, Marco Cecchini, Martin KarplusAbstract:Conformational Free-Energy differences are essential thermody- namic quantities for understanding the function of many biomolecules. They are accessible from computer simulations, but their accurate calculation is a challen- ging task. Here nonequilibrium computer simulations and the differential fluctua- tion theorem are used to evaluate the Free-Energy difference between two Conformational states of a structured miniprotein, the ! -hairpin of protein G, with an implicit treatment of the solvent. A molecular dynamics-based protocol is employed for the simulation of rapid switches between the Conformational states in both the forward and the reverse direction. From the work performed on the system in the individual switches, the Conformational Free-Energy difference is determined by use of the differential fluctuation theorem. The results are in excellent agreement with reference calculations from a long molecular dynamics simulation and from the confinement method. The nonequilibrium approach is a computationally efficient method for the calculation of Conformational Free- Energy differences for biological systems.
Charles L. Brooks - One of the best experts on this subject based on the ideXlab platform.
-
Coarse Grained Models Reveal Essential Contributions of Topological Constraints to the Conformational Free Energy of RNA Bulges
The journal of physical chemistry. B, 2014Co-Authors: Anthony M. Mustoe, Hashim M. Al-hashimi, Charles L. BrooksAbstract:Recent studies have shown that simple stereochemical constraints encoded at the RNA secondary structure level significantly restrict the orientation of RNA helices across two-way junctions and yield physically reasonable distributions of RNA 3D conformations. Here we develop a new coarse-grain model, TOPRNA, that is optimized for exploring detailed aspects of these topological constraints in complex RNA systems. Unlike prior models, TOPRNA effectively treats RNAs as collections of semirigid helices linked by Freely rotatable single strands, allowing us to isolate the effects of secondary structure connectivity and sterics on 3D structure. Simulations of bulge junctions show that TOPRNA captures new aspects of topological constraints, including variations arising from deviations in local A-form structure, translational displacements of the helices, and stereochemical constraints imposed by bulge-linker nucleotides. Notably, these aspects of topological constraints define Free Energy landscapes that coincid...
-
Coarse Grained Models Reveal Essential Contributions of Topological Constraints to the Conformational Free Energy of RNA Bulges
The Journal of Physical Chemistry, 2014Co-Authors: Anthony M. Mustoe, Hashim M. Al-hashimi, Charles L. BrooksAbstract:Recent studies have shown that simple stereochemical constraints encoded at the RNA secondary structure level significantly restrict the orientation of RNA helices across two-way junctions and yield physically reasonable distributions of RNA 3D conformations. Here we develop a new coarse-grain model, TOPRNA, that is optimized for exploring detailed aspects of these topological constraints in complex RNA systems. Unlike prior models, TOPRNA effectively treats RNAs as collections of semirigid helices linked by Freely rotatable single strands, allowing us to isolate the effects of secondary structure connectivity and sterics on 3D structure. Simulations of bulge junctions show that TOPRNA captures new aspects of topological constraints, including variations arising from deviations in local A-form structure, translational displacements of the helices, and stereochemical constraints imposed by bulge-linker nucleotides. Notably, these aspects of topological constraints define Free Energy landscapes that coincide with the distribution of bulge conformations in the PDB. Our simulations also quantitatively reproduce NMR RDC measurements made on HIV-1 TAR at low salt concentrations, although not for different TAR mutants or at high salt concentrations. Our results confirm that topological constraints are an important determinant of bulge conformation and dynamics and demonstrate the utility of TOPRNA for studying the topological constraints of complex RNAs.
Jeremy Esque - One of the best experts on this subject based on the ideXlab platform.
-
Accurate calculation of Conformational Free Energy differences in explicit water: the confinement-solvation Free Energy approach.
Journal of Physical Chemistry B, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly...
-
Accurate Calculation of Conformational Free Energy Differences in Explicit Water: The Confinement–Solvation Free Energy Approach B
The Journal of Physical Chemistry, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly converged Free-Energy results were obtained in agreement with equilibrium sampling or literature calculations. These results demonstrate that the CSF method may provide Conformational Free-Energy differences of biomolecules with small statistical errors (below 0.5 kcal/mol) and at a moderate computational cost even with a full representation of the solvent.
-
accurate calculation of Conformational Free Energy differences in explicit water the confinement solvation Free Energy approach b
The Journal of Physical Chemistry, 2015Co-Authors: Jeremy Esque, Marco CecchiniAbstract:The calculation of the Free Energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation Free Energy of the harmonically restrained conformers is accurately determined by multistage Free Energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation Free Energy (CSF) approach was used to compute differences in Free Energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, Conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly converged Free-Energy results were obtained in agreement with equilibrium sampling or literature calculations. These results demonstrate that the CSF method may provide Conformational Free-Energy differences of biomolecules with small statistical errors (below 0.5 kcal/mol) and at a moderate computational cost even with a full representation of the solvent.
Anthony M. Mustoe - One of the best experts on this subject based on the ideXlab platform.
-
Coarse Grained Models Reveal Essential Contributions of Topological Constraints to the Conformational Free Energy of RNA Bulges
The journal of physical chemistry. B, 2014Co-Authors: Anthony M. Mustoe, Hashim M. Al-hashimi, Charles L. BrooksAbstract:Recent studies have shown that simple stereochemical constraints encoded at the RNA secondary structure level significantly restrict the orientation of RNA helices across two-way junctions and yield physically reasonable distributions of RNA 3D conformations. Here we develop a new coarse-grain model, TOPRNA, that is optimized for exploring detailed aspects of these topological constraints in complex RNA systems. Unlike prior models, TOPRNA effectively treats RNAs as collections of semirigid helices linked by Freely rotatable single strands, allowing us to isolate the effects of secondary structure connectivity and sterics on 3D structure. Simulations of bulge junctions show that TOPRNA captures new aspects of topological constraints, including variations arising from deviations in local A-form structure, translational displacements of the helices, and stereochemical constraints imposed by bulge-linker nucleotides. Notably, these aspects of topological constraints define Free Energy landscapes that coincid...
-
Coarse Grained Models Reveal Essential Contributions of Topological Constraints to the Conformational Free Energy of RNA Bulges
The Journal of Physical Chemistry, 2014Co-Authors: Anthony M. Mustoe, Hashim M. Al-hashimi, Charles L. BrooksAbstract:Recent studies have shown that simple stereochemical constraints encoded at the RNA secondary structure level significantly restrict the orientation of RNA helices across two-way junctions and yield physically reasonable distributions of RNA 3D conformations. Here we develop a new coarse-grain model, TOPRNA, that is optimized for exploring detailed aspects of these topological constraints in complex RNA systems. Unlike prior models, TOPRNA effectively treats RNAs as collections of semirigid helices linked by Freely rotatable single strands, allowing us to isolate the effects of secondary structure connectivity and sterics on 3D structure. Simulations of bulge junctions show that TOPRNA captures new aspects of topological constraints, including variations arising from deviations in local A-form structure, translational displacements of the helices, and stereochemical constraints imposed by bulge-linker nucleotides. Notably, these aspects of topological constraints define Free Energy landscapes that coincide with the distribution of bulge conformations in the PDB. Our simulations also quantitatively reproduce NMR RDC measurements made on HIV-1 TAR at low salt concentrations, although not for different TAR mutants or at high salt concentrations. Our results confirm that topological constraints are an important determinant of bulge conformation and dynamics and demonstrate the utility of TOPRNA for studying the topological constraints of complex RNAs.
Klaus Lunkenheimer - One of the best experts on this subject based on the ideXlab platform.
-
influence of Conformational Free Energy of hydrocarbon chains on adsorption of nonionic surfactants at the air solution interface
Journal of Physical Chemistry B, 1999Co-Authors: Piotr Warszyński, Klaus LunkenheimerAbstract:The most frequently used theories of surfactant adsorption phenomena treat adsorbing molecules as structureless entities. However, surface active molecules consist of hydrophillic headgroups and hydrophobic chains. Therefore, surfactants have additional degrees of Freedom associated with conformations of the chains. An unrestricted hydrophobic chain can assume practically any conformation at the interface. Adsorption of other surfactant molecules provides restriction to the number of possible conformations changing the Conformational Free Energy. This change has to be reflected in the adsorption isotherm. We present a simple model of adsorption of soluble surfactants at the air/solution interface, taking explicitly into account the Conformational statistics of hydrophobic surfactant chains. The model is applied to describe adsorption isotherms of homologous series of dimethyl-n-alkyl phosphine oxides with the alkyl chain length of 7−13 carbon atoms.
-
Influence of Conformational Free Energy of Hydrocarbon Chains on Adsorption of Nonionic Surfactants at the Air/Solution Interface
The Journal of Physical Chemistry B, 1999Co-Authors: Piotr Warszyński, Klaus LunkenheimerAbstract:The most frequently used theories of surfactant adsorption phenomena treat adsorbing molecules as structureless entities. However, surface active molecules consist of hydrophillic headgroups and hydrophobic chains. Therefore, surfactants have additional degrees of Freedom associated with conformations of the chains. An unrestricted hydrophobic chain can assume practically any conformation at the interface. Adsorption of other surfactant molecules provides restriction to the number of possible conformations changing the Conformational Free Energy. This change has to be reflected in the adsorption isotherm. We present a simple model of adsorption of soluble surfactants at the air/solution interface, taking explicitly into account the Conformational statistics of hydrophobic surfactant chains. The model is applied to describe adsorption isotherms of homologous series of dimethyl-n-alkyl phosphine oxides with the alkyl chain length of 7−13 carbon atoms.