Latest Articles of Journal of Chemical Information and Modeling


Holistic Approach to Partial Covalent Interactions in Protein Structure Prediction and Design with Rosetta 10.1021/acs.jcim.7b00398 2018-04-19 Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation−π, and π–π interactions, contribute to thermodynamic stability and facilitate interactions with other biomolecules. Several score functions have been develope...
Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models 10.1021/acs.jcim.8b00026 2018-04-18 Thermodynamic and kinetic properties are of critical importance for the applicability of computational models to biomolecules such as proteins. Here we present an extensive evaluation of the Amber ff99SB-ILDN force field for modeling of hydration and diffusio...
Role of Molecular Interactions and Protein Rearrangement in the Dissociation Kinetics of p38α MAP Kinase Type-I/II/III Inhibitors 10.1021/acs.jcim.7b00640 2018-04-16 Understanding the governing factors of fast or slow inhibitor binding/unbinding assists in developing drugs with preferred kinetic properties. For inhibitors with the same binding affinity targeting different binding sites of the same protein, the kinetic beh...
Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization 10.1021/acs.jcim.8b00097 2018-04-13 Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that ...
ReFlex3D: Refined Flexible Alignment of Molecules Using Shape and Electrostatics 10.1021/acs.jcim.7b00618 2018-04-13 We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay betwee...
Large-Scale Validation of Mixed-Solvent Simulations to Assess Hotspots at Protein–Protein Interaction Interfaces 10.1021/acs.jcim.7b00487 2018-04-11 The ability to target protein–protein interactions (PPIs) with small molecule inhibitors offers great promise in expanding the druggable target space and addressing a broad range of untreated diseases. However, due to their nature and function of interacting ...
Dissecting the Innate Immune Recognition of Opioid Inactive Isomer (+)-Naltrexone Derived Toll-like Receptor 4 (TLR4) Antagonists 10.1021/acs.jcim.7b00717 2018-04-11 The opioid inactive isomer (+)-naltrexone is one of the rare Toll-like receptor 4 (TLR4) antagonists with good blood–brain barrier (BBB) permeability, which is a lead with promising potential for treating neuropathic pain and drug addiction. (+)-Naltrexone ta...
Virtual Screening of Novel and Selective Inhibitors of Protein Tyrosine Phosphatase 1B over T-Cell Protein Tyrosine Phosphatase Using a Bidentate Inhibition Strategy 10.1021/acs.jcim.8b00040 2018-04-05 Protein tyrosine phosphatase 1B (PTP1B), a promising target for type II diabetes, obesity, and cancer therapeutics, plays an important negative role in insulin signaling pathways. However, the lack of selectivity over other PTPs, especially for T-cell protein...
Incorporation of Hydrogen Bond Angle Dependency into the Generalized Solvation Free Energy Density Model 10.1021/acs.jcim.7b00410 2018-03-30 To describe the physically realistic solvation free energy surface of a molecule in a solvent, a generalized version of the solvation free energy density (G-SFED) calculation method has been developed. In the G-SFED model, the contribution from the hydrogen b...
Structural Investigation of the Dopamine-2 Receptor Agonist Bromocriptine Binding to Dimeric D2HighR and D2LowR States 10.1021/acs.jcim.7b00722 2018-03-29 The active (D2HighR) and inactive (D2LowR) states of dimeric dopamine D2 receptor (D2R) models were investigated to clarify the binding mechanisms of the dopamine agonist bromocriptine, using Molecular Dynamics (MD) simulation. The aim of this comprehensive s...

Holistic Approach to Partial Covalent Interactions in Protein Structure Prediction and Design with Rosetta

10.1021/acs.jcim.7b00398

2018-04-19

Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation−π, and π–π interactions, contribute to thermodynamic stability and facilitate interactions with other biomolecules. Several score functions have been develope...

Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models

10.1021/acs.jcim.8b00026

2018-04-18

Thermodynamic and kinetic properties are of critical importance for the applicability of computational models to biomolecules such as proteins. Here we present an extensive evaluation of the Amber ff99SB-ILDN force field for modeling of hydration and diffusio...

Role of Molecular Interactions and Protein Rearrangement in the Dissociation Kinetics of p38α MAP Kinase Type-I/II/III Inhibitors

10.1021/acs.jcim.7b00640

2018-04-16

Understanding the governing factors of fast or slow inhibitor binding/unbinding assists in developing drugs with preferred kinetic properties. For inhibitors with the same binding affinity targeting different binding sites of the same protein, the kinetic beh...

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization

10.1021/acs.jcim.8b00097

2018-04-13

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that ...

ReFlex3D: Refined Flexible Alignment of Molecules Using Shape and Electrostatics

10.1021/acs.jcim.7b00618

2018-04-13

We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay betwee...

Large-Scale Validation of Mixed-Solvent Simulations to Assess Hotspots at Protein–Protein Interaction Interfaces

10.1021/acs.jcim.7b00487

2018-04-11

The ability to target protein–protein interactions (PPIs) with small molecule inhibitors offers great promise in expanding the druggable target space and addressing a broad range of untreated diseases. However, due to their nature and function of interacting ...

Dissecting the Innate Immune Recognition of Opioid Inactive Isomer (+)-Naltrexone Derived Toll-like Receptor 4 (TLR4) Antagonists

10.1021/acs.jcim.7b00717

2018-04-11

The opioid inactive isomer (+)-naltrexone is one of the rare Toll-like receptor 4 (TLR4) antagonists with good blood–brain barrier (BBB) permeability, which is a lead with promising potential for treating neuropathic pain and drug addiction. (+)-Naltrexone ta...

Virtual Screening of Novel and Selective Inhibitors of Protein Tyrosine Phosphatase 1B over T-Cell Protein Tyrosine Phosphatase Using a Bidentate Inhibition Strategy

10.1021/acs.jcim.8b00040

2018-04-05

Protein tyrosine phosphatase 1B (PTP1B), a promising target for type II diabetes, obesity, and cancer therapeutics, plays an important negative role in insulin signaling pathways. However, the lack of selectivity over other PTPs, especially for T-cell protein...

Incorporation of Hydrogen Bond Angle Dependency into the Generalized Solvation Free Energy Density Model

10.1021/acs.jcim.7b00410

2018-03-30

To describe the physically realistic solvation free energy surface of a molecule in a solvent, a generalized version of the solvation free energy density (G-SFED) calculation method has been developed. In the G-SFED model, the contribution from the hydrogen b...

Structural Investigation of the Dopamine-2 Receptor Agonist Bromocriptine Binding to Dimeric D2HighR and D2LowR States

10.1021/acs.jcim.7b00722

2018-03-29

The active (D2HighR) and inactive (D2LowR) states of dimeric dopamine D2 receptor (D2R) models were investigated to clarify the binding mechanisms of the dopamine agonist bromocriptine, using Molecular Dynamics (MD) simulation. The aim of this comprehensive s...