Free energy perturbation
View article: Accurate Predictionof Drug Resistance for IntrinsicallyDisordered Protein Regions
Accurate Predictionof Drug Resistance for IntrinsicallyDisordered Protein Regions Open
Relative alchemical binding free energy calculations can be used to predict the effect of amino acid mutations on ligand binding affinities. However, these protocols are not well established for proteins containing intrinsically disordered…
View article: Synergistic Computational Approaches for Accelerated Drug Discovery: Integrating Quantum Mechanics, Statistical Thermodynamics, and Quantum Computing
Synergistic Computational Approaches for Accelerated Drug Discovery: Integrating Quantum Mechanics, Statistical Thermodynamics, and Quantum Computing Open
Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and diff…
View article: Synergistic Computational Approaches for Accelerated Drug Discovery: Integrating Quantum Mechanics, Statistical Thermodynamics, and Quantum Computing
Synergistic Computational Approaches for Accelerated Drug Discovery: Integrating Quantum Mechanics, Statistical Thermodynamics, and Quantum Computing Open
Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and diff…
View article: Identification of covalent and non-peptidomimetic plasmepsin V inhibitors as potential antimalarial leads
Identification of covalent and non-peptidomimetic plasmepsin V inhibitors as potential antimalarial leads Open
The proposed project targets PM V for highly selective inhibitor design as it is the most structurally distinct enzyme from both Plasmodium and human aspartic proteases. Two approaches will be applied: (i) screening for non-peptidomimetic …
View article: Identification of covalent and non-peptidomimetic plasmepsin V inhibitors as potential antimalarial leads
Identification of covalent and non-peptidomimetic plasmepsin V inhibitors as potential antimalarial leads Open
The proposed project targets PM V for highly selective inhibitor design as it is the most structurally distinct enzyme from both Plasmodium and human aspartic proteases. Two approaches will be applied: (i) screening for non-peptidomimetic …
View article: Comparing ForceField Treatments in QM/MM Studiesof the SARS-CoV‑2 RNA-Dependent RNA Polymerase (RdRp) Mechanism
Comparing ForceField Treatments in QM/MM Studiesof the SARS-CoV‑2 RNA-Dependent RNA Polymerase (RdRp) Mechanism Open
Molecular simulations have been instrumental in elucidating the SARS-CoV-2 lifecycle, thereby supporting the design and development of antiviral therapies and diagnostic tools for COVID-19. Here, the molecular mechanism of the SARS-CoV-2 R…
View article: Comparing ForceField Treatments in QM/MM Studiesof the SARS-CoV‑2 RNA-Dependent RNA Polymerase (RdRp) Mechanism
Comparing ForceField Treatments in QM/MM Studiesof the SARS-CoV‑2 RNA-Dependent RNA Polymerase (RdRp) Mechanism Open
Molecular simulations have been instrumental in elucidating the SARS-CoV-2 lifecycle, thereby supporting the design and development of antiviral therapies and diagnostic tools for COVID-19. Here, the molecular mechanism of the SARS-CoV-2 R…
View article: Free Energy Analysis of Co-Solvent Induced Solvation Changes in Binary Mixtures
Free Energy Analysis of Co-Solvent Induced Solvation Changes in Binary Mixtures Open
Understanding the influence of co-solvents on solvation thermodynamics in binary liquid mixtures is essential for controlling solution behavior in chemical, biological, and industrial systems. This study presents a comprehensive free energ…
View article: Free Energy Analysis of Co-Solvent Induced Solvation Changes in Binary Mixtures
Free Energy Analysis of Co-Solvent Induced Solvation Changes in Binary Mixtures Open
Understanding the influence of co-solvents on solvation thermodynamics in binary liquid mixtures is essential for controlling solution behavior in chemical, biological, and industrial systems. This study presents a comprehensive free energ…
View article: Repurposed Arylidene-hydrazinyl-1,3-thiazolesas MultitargetAnti-Alzheimer’s Agents via Combined Computational and ExperimentalStudies
Repurposed Arylidene-hydrazinyl-1,3-thiazolesas MultitargetAnti-Alzheimer’s Agents via Combined Computational and ExperimentalStudies Open
In quest of new and potent multitarget therapeutics for Alzheimer’s disease (AD), a series of recently synthesized arylidene-hydrazinyl-thiazoles were repurposed as multitarget directed anti-AD agents. In total, 14 compounds were tested fo…
View article: Computational Analysis of GAT1 Mutations: Functional Consequences from Molecular Dynamics and Binding Free Energy Calculations
Computational Analysis of GAT1 Mutations: Functional Consequences from Molecular Dynamics and Binding Free Energy Calculations Open
GABA transporter 1 (GAT1), encoded by the SLC6A1 gene, is essential for maintaining inhibitory neurotransmission by mediating the reuptake of GABA from the synaptic cleft. Dysfunction of GAT1 has been linked to several neurological and neu…
View article: Quantum Monte Carlo with Fortran (QmcFort)
Quantum Monte Carlo with Fortran (QmcFort) Open
QmcFort is an open-source software package for performing Auxiliary-Field Quantum Monte Carlo (AFQMC) calculations. Written in modern Fortran, it is designed for high-accuracy electronic structure simulations and achieves near-peak perform…
View article: Quantum Monte Carlo with Fortran (QmcFort)
Quantum Monte Carlo with Fortran (QmcFort) Open
QmcFort is an open-source software package for performing Auxiliary-Field Quantum Monte Carlo (AFQMC) calculations. Written in modern Fortran, it is designed for high-accuracy electronic structure simulations and achieves near-peak perform…
View article: Thermokinetic Studyof Triplet CH<sub>3</sub>OH +CH<sub>2</sub>: A New Approach for Complexation Free Energy
Thermokinetic Studyof Triplet CH<sub>3</sub>OH +CH<sub>2</sub>: A New Approach for Complexation Free Energy Open
This study provides novel insights into the methanol (CH3OH) + methylene (CH2) reaction dynamics, introducing the complexation energy and the complexation free energy to characterize prereactive complex formation in t…
View article: QligFEP-2: an automated workflow for small molecule free energy calculations in Q
QligFEP-2: an automated workflow for small molecule free energy calculations in Q Open
Predicting how chemical modifications affect drug binding is central to rational drug design. Free Energy Perturbation (FEP) calculations provide accurate estimates of these binding affinity changes, but existing methods often require subs…
View article: Accurate predictions of protein mutational effects accelerated with a hybrid-topology free energy protocol
Accurate predictions of protein mutational effects accelerated with a hybrid-topology free energy protocol Open
Quantifying the effects of point mutations is of utmost interest for pharmaceutical and biotechnological applications. Reliable computational methods range from statistical and AI-based to physics-based approaches, with the optimal balance…
View article: QligFEP-2: an automated workflow for small molecule free energy calculations in Q
QligFEP-2: an automated workflow for small molecule free energy calculations in Q Open
Predicting how chemical modifications affect drug binding is central to rational drug design. Free Energy Perturbation (FEP) calculations provide accurate estimates of these binding affinity changes, but existing methods often require subs…
View article: Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase
Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase Open
The discovery of urethanases shows an opportunity to access the biotechnological recycling of polyurethane-based plastics (PURs), widely used in the manufacture of everyday materials. However, the mechanistic understanding of these enzymes…
View article: Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase
Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase Open
The discovery of urethanases shows an opportunity to access the biotechnological recycling of polyurethane-based plastics (PURs), widely used in the manufacture of everyday materials. However, the mechanistic understanding of these enzymes…
View article: Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase
Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase Open
The discovery of urethanases shows an opportunity to access the biotechnological recycling of polyurethane-based plastics (PURs), widely used in the manufacture of everyday materials. However, the mechanistic understanding of these enzymes…
View article: Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase
Insights into the CatalyticActivity of a Metagenome-DerivedUrethanase Open
The discovery of urethanases shows an opportunity to access the biotechnological recycling of polyurethane-based plastics (PURs), widely used in the manufacture of everyday materials. However, the mechanistic understanding of these enzymes…
View article: Path Integral‐Free Energy Perturbation ( <scp>PI</scp> ‐ <scp>FEP</scp> ) Simulations: Kinetic Isotope Effects of Proton/Deuteron Transfer Reactions in Aqueous Solution
Path Integral‐Free Energy Perturbation ( <span>PI</span> ‐ <span>FEP</span> ) Simulations: Kinetic Isotope Effects of Proton/Deuteron Transfer Reactions in Aqueous Solution Open
We present a tutorial review of the theoretical background and a step‐by‐step computational procedure for determining kinetic isotope effects (KIEs) of chemical reactions in aqueous solution. The method combines path integral and free ener…
View article: First-Order PerturbationTheory for Associating Fluidsin the Isothermal–Isobaric Ensemble
First-Order PerturbationTheory for Associating Fluidsin the Isothermal–Isobaric Ensemble Open
In this study, we invert Wertheim’s first-order thermodynamic perturbation theory (TPT1) to the isothermal–isobaric ensemble (NPT) for a hard-sphere reference system. The inversion is conducted using exact relationships that …
View article: Defining the pH* Scale in Methanol: Determinationof Accurate Values for the Solvation Free Energies of CH<sub>3</sub>OH<sub>2</sub><sup>+</sup> and CH<sub>3</sub>O<sup>–</sup> in Methanol
Defining the pH* Scale in Methanol: Determinationof Accurate Values for the Solvation Free Energies of CH<sub>3</sub>OH<sub>2</sub><sup>+</sup> and CH<sub>3</sub>O<sup>–</sup> in Methanol Open
A correction factor for the autoprotolysis constant of methanol is proposed in the present work to obtain thermodynamic data for the standard solvation free energies of CH3OH2+ and CH3O–
View article: Free Energy PerturbationSimulations Measure the Changein Binding Affinity of the Aβ25–35 Peptide to the ZwitterionicBilayer Caused by Oxidation
Free Energy PerturbationSimulations Measure the Changein Binding Affinity of the Aβ25–35 Peptide to the ZwitterionicBilayer Caused by Oxidation Open
We designed and employed a relative free energy perturbation (FEP) combined with replica exchange with solute tempering (REST) all-atom molecular dynamics to investigate how Met35 oxidation affects the free energy of binding of the Aβ25–35…
View article: Benchmarking Alchemical Relative Binding Free EnergyCalculations for Nucleotide Binding to Multimeric ATPases
Benchmarking Alchemical Relative Binding Free EnergyCalculations for Nucleotide Binding to Multimeric ATPases Open
Multimeric ATPases generally bind nucleotides at intersubunit interfaces, where cooperative or allosteric interactions complicate experimental measurement of binding affinities. Here, we present a large-scale benchmarking study of alchemic…
View article: Can ElectrostaticSolvation Entropy Predict Skin IrritationPotential from Surfactants?
Can ElectrostaticSolvation Entropy Predict Skin IrritationPotential from Surfactants? Open
Surfactants are essential in industrial and biological applications, but their interactions with biological systems, particularly skin, often lead to irritation. Understanding the molecular determinants of surfactant-induced skin irritatio…
View article: Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations
Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations Open
Free energies of solvation in water and liquid cyclohexane have been computed for 20 arenes ranging in size from cyclobutadiene to coronene. Monte Carlo statistical mechanics (MC) was used with free-energy perturbation theory (FEP) and the…
View article: Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations
Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations Open
Free energies of solvation in water and liquid cyclohexane have been computed for 20 arenes ranging in size from cyclobutadiene to coronene. Monte Carlo statistical mechanics (MC) was used with free-energy perturbation theory (FEP) and the…
View article: Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations
Polycyclic AromaticHydrocarbons: Solvation, Solubility,and Hydrophobic Effects from Monte Carlo Simulations Open
Free energies of solvation in water and liquid cyclohexane have been computed for 20 arenes ranging in size from cyclobutadiene to coronene. Monte Carlo statistical mechanics (MC) was used with free-energy perturbation theory (FEP) and the…