ArticleJournal of chemical information and modeling2014
Parameter choice matters: validating probe parameters for use in mixed-solvent simulations.
Article in Journal of chemical information and modeling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Mixed-Solvent MD suite: modular tools for building and analyzing mixed-solvent molecular dynamics systems.Journal of computer-aided molecular design · 2026Article
- Accelerating fragment-based drug discovery using grand canonical nonequilibrium candidate Monte Carlo.Nature communications · 2025Article
- Recent computational advances in the identification of cryptic binding sites for drug discovery.Bioinformatics advances · 2025Review
- CosolvKit: a Versatile Tool for Cosolvent MD Preparation and Analysis.Journal of chemical information and modeling · 2024Article
- Enhancing SILCS-MC via GPU Acceleration and Ligand Conformational Optimization with Genetic and Parallel Tempering Algorithms.The journal of physical chemistry. B · 2024Article
- Application of Mixed-Solvent Molecular Dynamics Simulations for Prediction of Allosteric Sites on G Protein-Coupled Receptors.Molecular pharmacology · 2023Article
- Discovery of the Cryptic Sites of SARS-CoV-2 Papain-like Protease and Analysis of Its Druggability.International journal of molecular sciences · 2022Article
- Computational Identification of Possible Allosteric Sites and Modulators of the SARS-CoV-2 Main Protease.Journal of chemical information and modeling · 2022Article
- Identification of Cryptic Binding Sites Using MixMD with Standard and Accelerated Molecular Dynamics.Journal of chemical information and modeling · 2021Article
- Chemical validation of a druggable site on Hsp27/HSPB1 using in silico solvent mapping and biophysical methods.Bioorganic & medicinal chemistry · 2021Article
- Structural resolution of switchable states of a de novo peptide assembly.Nature communications · 2021Article
- Modeling Epac1 interactions with the allosteric inhibitor AM-001 by co-solvent molecular dynamics.Journal of computer-aided molecular design · 2020Article
- Screening of Natural Products Targeting SARS-CoV-2-ACE2 Receptor Interface - A MixMD Based HTVS Pipeline.Frontiers in chemistry · 2020Article
- K-RasBiochemistry · 2019Article
- Free Energies and Entropies of Binding Sites Identified by MixMD Cosolvent Simulations.Journal of chemical information and modeling · 2019Article
- Solvents to Fragments to Drugs: MD Applications in Drug Design.Molecules (Basel, Switzerland) · 2018Review
- MixMD Probeview: Robust Binding Site Prediction from Cosolvent Simulations.Journal of chemical information and modeling · 2018Article
- Predicting Displaceable Water Sites Using Mixed-Solvent Molecular Dynamics.Journal of chemical information and modeling · 2018Article
- Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations.Journal of chemical theory and computation · 2017Article
- Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.Journal of medicinal chemistry · 2016Review
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Authors and funding
3 authors.
Funding
Abstract
Probe mapping is a common approach for identifying potential binding sites in structure-based drug design; however, it typically relies on energy minimizations of probes in the gas phase and a static protein structure. The mixed-solvent molecular dynamics (MixMD) approach was recently developed to account for full protein flexibility and solvation effects in hot-spot mapping. Our first study used only acetonitrile as a probe, and here, we have augmented the set of functional group probes through careful testing and parameter validation. A diverse range of probes are needed in order to map complex binding interactions. A small variation in probe parameters can adversely effect mixed-solvent behavior, which we highlight with isopropanol. We tested 11 solvents to identify six with appropriate behavior in TIP3P water to use as organic probes in the MixMD method. In addition to acetonitrile and isopropanol, we have identified acetone, N-methylacetamide, imidazole, and pyrimidine. These probe solvents will enable MixMD studies to recover hydrogen-bonding sites, hydrophobic pockets, protein-protein interactions, and aromatic hotspots. Also, we show that ternary-solvent systems can be incorporated within a single simulation. Importantly, these binary and ternary solvents do not require artificial repulsion terms like other methods. Within merely 5 ns, layered solvent boxes become evenly mixed for soluble probes. We used radial distribution functions to evaluate solvent behavior, determine adequate mixing, and confirm the absence of phase separation. We recommend that radial distribution functions should be used to assess adequate sampling in all mixed-solvent techniques rather than the current practice of examining the solvent ratios at the edges of the solvent box.
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