A5059672458- Protein Structure and Dynamics
- Various Chemistry Research Topics
- Machine Learning in Materials Science
- Computational Drug Discovery Methods
- Ion channel regulation and function
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Fuel Cells and Related Materials
- Cardiac electrophysiology and arrhythmias
- Chemical Thermodynamics and Molecular Structure
- Spectroscopy and Quantum Chemical Studies
- Force Microscopy Techniques and Applications
- Advanced Physical and Chemical Molecular Interactions
- Muon and positron interactions and applications
- Advanced Electron Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Protein Interaction Studies and Fluorescence Analysis
- Acoustic Wave Resonator Technologies
- Asymmetric Hydrogenation and Catalysis
- Genetics, Bioinformatics, and Biomedical Research
- Advanced Chemical Physics Studies
- Electrochemical Analysis and Applications
- History and advancements in chemistry
University of California, Irvine
2017-2021
Vanderbilt University
2016
Traditional approaches to specifying a molecular mechanics force field encode all the information needed assign parameters given molecule into discrete set of atom types. This is equivalent representation consisting graph comprising vertices, which represent atoms labeled by type, and unlabeled edges, chemical bonds. Bond stretch, angle bend, dihedral are then assigned looking up bonded pairs, triplets, quartets types in parameter tables valence terms using themselves nonbonded parameters....
We present a methodology for defining and optimizing general force field classical molecular simulations, we describe its use to derive the Open Force Field 1.0.0 small-molecule field, codenamed Parsley. Rather than using traditional atom typing, our approach is built on SMIRKS-native (SMIRNOFF) parameter assignment formalism, which handles increases in diversity specificity of definition without needlessly increasing complexity specification. Parameters are optimized with ForceBalance tool,...
Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality these relies the force to represent systems.
Abstract Here, we focus on testing and improving force fields for molecular modeling, which see widespread use in diverse areas of computational chemistry biomolecular simulation. A key issue affecting the accuracy transferrability these is atom typing. Traditional approaches to defining mechanics must encode, within a discrete set types, all information will ever be needed about chemical environment; parameters are then assigned by looking up combinations types tables. This typing approach...
We describe the structure and optimization of Open Force Field 1.0.0 small molecule force field, code-named Parsley. Parsley uses SMIRKS-native (SMIRNOFF) parameter assignment formalism in which types are assigned directly by chemical perception, contrast to traditional atom type-based approaches. This method provides a natural means incorporate increasingly diverse chemistry without needlessly increasing field complexity. In this work, we present essentially full valence parameters field....
We present a methodology for defining and optimizing general force field classical molecular simulations, we describe its use to derive the Open Force Field 1.0.0 small molecule field, code-named Parsley. Rather than traditional atom-typing, our approach builds on SMIRKS-native (SMIRNOFF) parameter assignment formalism, which handles increases in diversity specificity of definition without needlessly increasing complexity specification. Parameters are optimized with ForceBalance tool, based...
The human voltage-gated proton channel Hv1 is a drug target for cancer, ischemic stroke, and neuroinflammation. It resides on the plasma membrane endocytic compartments of variety cell types, where it mediates outward movement regulates activity NOX enzymes. Its voltage-sensing domain (VSD) contains gated proton-selective conduction pathway, which can be blocked by aromatic guanidine derivatives such as 2-guanidinobenzimidazole (2GBI). Mutation residue F150 to alanine (F150A) was previously...
Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality these relies the force to represent systems. Focusing small molecules fewer than 50 heavy atoms, our aim this work is compare six fields: GAFF, GAFF2, MMFF94, MMFF94S, SMIRNOFF99Frosst, Open Field version 1.0 (Parsley) field. On dataset comprising over 26,000 structures, we analyzed their...
Accurate hydrogen placement in molecular modeling is crucial for studying the interactions and dynamics of biomolecular systems. The carboxyl functional group a prototypical example that requires protonation during structure preparation. To our knowledge, when their neutral form, carboxylic acids are typically protonated syn conformation by default classical packages, with no consideration alternative conformations, though we not aware any careful examination this topic. Here, investigate...
Voltage-gated sodium, potassium, and calcium channels consist of four voltage-sensing domains (VSDs) that surround a central pore domain transition from down state to an up in response membrane depolarization. While many types drugs bind domains, the number organic molecules known VSDs is limited. The Hv1 voltage-gated proton channel made two does not contain domain, providing simplified model for studying how small ligands interact with VSDs. Here, we describe ligand, named HIF, interacts...
Abstract Hv1 is a voltage-gated proton channel whose main function to facilitate extrusion of protons from the cell. The development effective blockers for can lead new therapeutics treatment maladies related dysfunction. Although mechanism permeation in remains be elucidated, series small molecules have been discovered inhibit Hv1. Here, we computed relative binding free energies prototypical blocker on model human an open state. We used alchemical energy perturbation techniques based...
Force fields are used in a wide variety of contexts for classical molecular simulation, including studies on protein-ligand binding, membrane permeation, and thermophysical property prediction. The quality these relies the force to represent systems. Focusing small molecules fewer than 50 heavy atoms, our aim this work is compare nine fields: GAFF, GAFF2, MMFF94, MMFF94S, OPLS3e, SMIRNOFF99Frosst, Open Field Parsley, versions 1.0, 1.1 1.2. On dataset comprising 22,675 structures 3,271...
We present a methodology for defining and optimizing general force field classical molecular simulations, we describe its use to derive the Open Force Field 1.0.0 small molecule field, code-named Parsley. Rather than traditional atom-typing, our approach builds on SMIRKS-native (SMIRNOFF) parameter assignment formalism, which handles increases in diversity specificity of definition without needlessly increasing complexity specification. Parameters are optimized with ForceBalance tool, based...
Many molecular simulation methods use force fields to help model and simulate molecules their behavior in various environments. Force are sets of functions parameters used calculate the potential energy a chemical system as function atomic coordinates. Despite widespread fields, inadequacies often thought contribute systematic errors simulations. Furthermore, different tend give varying results on same systems with settings. Here, we present pipeline for comparing geometries small molecule...
Many molecular simulation methods use force fields to help model and simulate molecules their behavior in various environments. Force are sets of functions parameters used calculate the potential energy a chemical system as function atomic coordinates. Despite widespread fields, inadequacies often thought contribute systematic errors simulations. Furthermore, different tend give varying results on same systems with settings. Here, we present pipeline for comparing geometries small molecule...
We describe the structure and optimization of Open Force Field 1.0.0 small molecule force field, code-named Parsley. Parsley uses SMIRKS-native (SMIRNOFF) parameter assignment formalism in which types are assigned directly by chemical perception, contrast to traditional atom type-based approaches. This method provides a natural means incorporate increasingly diverse chemistry without needlessly increasing field complexity. In this work, we present essentially full valence parameters field....