scholarly journals Molecular Level Understanding of the Free Energy Landscape in Early Stages of MOF Nucleation

2019 ◽  
Author(s):  
Loukas Kollias ◽  
David C. Cantu ◽  
Marcus A. Tubbs ◽  
Roger Rousseau ◽  
Vassiliki-Alexandra Glezakou ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Level ◽  
Salt Bridges ◽  
Enhanced Sampling ◽  
Material Synthesis ◽  
Early Stages ◽  
Assembly Mechanism ◽  
Secondary Building Units ◽  
Molecular Dynamics Methods ◽  
Shed Light

<div><div><div><p>The assembly mechanism of hierarchical materials controlled by the choice of solvent and presence of spectator ions. In this paper, we use enhanced sampling molecular dynamics methods to investigate these effects on the configurational landscape of metal-linker interactions in the early stages of synthesis, using MIL-101(Cr) as a prototypical example. Microsecond-long well- tempered metadynamics (WTmetaD) simulations uncover a complex free energy structural landscape, with distinct crystal (C) and non-crystal (NC) like configurations and their equilibrium population. In presence of ions (Na+, F-), we observe a complex effect on the crystallinity of secondary building units (SBUs), by encouraging/suppressing salt bridges between C configurations and consequently controlling the percentage of defects. Solvent effects are assessed by introducing N, N dimethylformamide (DMF) instead of water, where SBU adducts are appreciably more stable and compact. These results shed light on how solvent and ionic strength impact the free energy of assembly phenomena that ultimately control material synthesis</p></div></div></div>

scholarly journals Molecular Level Understanding of the Free Energy Landscape in Early Stages of MOF Nucleation

2019 ◽  
Author(s):  
Loukas Kollias ◽  
David C. Cantu ◽  
Marcus A. Tubbs ◽  
Roger Rousseau ◽  
Vassiliki-Alexandra Glezakou ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Level ◽  
Salt Bridges ◽  
Enhanced Sampling ◽  
Material Synthesis ◽  
Early Stages ◽  
Assembly Mechanism ◽  
Secondary Building Units ◽  
Molecular Dynamics Methods ◽  
Shed Light

<div><div><div><p>The assembly mechanism of hierarchical materials controlled by the choice of solvent and presence of spectator ions. In this paper, we use enhanced sampling molecular dynamics methods to investigate these effects on the configurational landscape of metal-linker interactions in the early stages of synthesis, using MIL-101(Cr) as a prototypical example. Microsecond-long well- tempered metadynamics (WTmetaD) simulations uncover a complex free energy structural landscape, with distinct crystal (C) and non-crystal (NC) like configurations and their equilibrium population. In presence of ions (Na+, F-), we observe a complex effect on the crystallinity of secondary building units (SBUs), by encouraging/suppressing salt bridges between C configurations and consequently controlling the percentage of defects. Solvent effects are assessed by introducing N, N dimethylformamide (DMF) instead of water, where SBU adducts are appreciably more stable and compact. These results shed light on how solvent and ionic strength impact the free energy of assembly phenomena that ultimately control material synthesis</p></div></div></div>

scholarly journals Molecular Level Understanding of the Free Energy Landscape in Early Stages of MOF Nucleation

2018 ◽  
Author(s):  
Loukas Kollias ◽  
David C. Cantu ◽  
Marcus A. Tubbs ◽  
Roger Rousseau ◽  
Vassiliki-Alexandra Glezakou ◽  
...  
Keyword(s):  
Free Energy ◽  
Defect Formation ◽  
Dimethyl Formamide ◽  
Salt Bridges ◽  
Enhanced Sampling ◽  
Materials Synthesis ◽  
Early Stages ◽  
Assembly Mechanism ◽  
Secondary Building Units ◽  
Molecular Dynamics Methods

<div><div><div><p>The assembly mechanism of hierarchical materials controlled by the choice of solvent and presence of spectator ions. In this paper, we use enhanced sampling molecular dynamics methods to investigate these effects on the configurational landscape of metal-linker interactions in the early stages of synthesis, using MIL-101(Cr) as a prototypical example. Microsecond-long well-tempered metadynamics (WTmetaD) simulations uncover a complex free energy structural landscape, with distinct crystal (C) and non-crystal (NC) like configurations and their equilibrium population. In presence of ions (Na+, F-), we observe a complex effect on the crystallinity of secondary building units (SBUs), by encouraging/suppressing salt bridges between C configurations and consequently controlling the percentage of defects. Solvent effects are assessed by introducing N, N dimethyl formamide (DMF) instead of water, where SBU adducts are appreciably more stable and compact. These results shed light on how solvent and ionic strength impact the free energy of assembly phenomena that ultimately control materials synthesis and defect formation.</p></div></div></div>

scholarly journals Molecular Level Understanding of the Free Energy Landscape in Early Stages of Metal–Organic Framework Nucleation

2019 ◽  
Vol 141 (14) ◽  
pp. 6073-6081 ◽  
Author(s):  
Loukas Kollias ◽  
David C. Cantu ◽  
Marcus A. Tubbs ◽  
Roger Rousseau ◽  
Vassiliki-Alexandra Glezakou ◽  
...  
Keyword(s):  
Free Energy ◽  
Molecular Level ◽  
Metal Organic Framework ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Early Stages ◽  
Metal Organic ◽  
Organic Framework

scholarly journals Multi-Funnel Landscape of the Fold-Switching Protein RfaH-CTD

2017 ◽  
Author(s):  
Nathan A. Bernhardt ◽  
Ulrich H.E. Hansmann
Keyword(s):  
Free Energy ◽  
Transcription Factor ◽  
Biological Function ◽  
Double Helix ◽  
Energy Landscape ◽  
Three Dimensional ◽  
Conversion Process ◽  
Free Energy Landscape ◽  
Enhanced Sampling ◽  
Helix Bundle

AbstractProteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle, and promotes translation when this domain assumes a β-barrel form. This fold-switch has been also observed for the isolated domain, dubbed by us RfaH-CTD, and is studied here with a variant of the RET approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free energy landscape of RfaH-CTD and to propose a mechanism for the conversion process.TOC Image

scholarly journals Potential Drug Candidates for SARS-CoV-2 Using Computational Screening and Enhanced Sampling Methods

2020 ◽  
Author(s):  
Sadanandam Namsani ◽  
Debabrata Pramanik ◽  
Mohd Aamir Khan ◽  
Sudip Roy ◽  
Jayant Singh
Keyword(s):  
Free Energy ◽  
High Performance ◽  
Search Space ◽  
Computational Method ◽  
Enhanced Sampling ◽  
Free Energy Surface ◽  
Drug Candidates ◽  
Drug Molecules ◽  
Computational Screening ◽  
Graphical Processing

<div><div><div><p>Here we report new chemical entities that are highly specific in binding towards the 3-chymotrypsin- like cysteine protease (3CLpro) protein present in the novel SARS-CoV2 virus. The viral 3CLpro</p><p>protein controls coronavirus replication. Therefore, 3CLpro is identified as a target for drug molecules. We have implemented an enhanced sampling method in combination with molecular dynamics and docking to bring down the computational screening search space to four molecules that could be synthesised and tested against COVID-19. Our computational method is much more robust than any other method available for drug screening e.g., docking, because of sampling of the free energy surface of the binding site of the protein (including the ligand) and use of explicit solvent. We have considered all possible interactions between all the atoms present in the protein, ligands, and water. Using high performance computing with graphical processing units we are able to perform large number of simulations within a month's time and converge to 4 most strongly bound ligands (by free energy and other scores) from a set of 17 ligands with lower docking scores. Based on our results and analysis, we claim with high confidence, that we have identified four potential ligands. Out of those, one particular ligand is the most promising candidate, based on free energy data, for further synthesis and testing against SARS-CoV-2 and might be effective for the cure of COVID-19.</p></div></div></div>

scholarly journals Enhancing Water Sampling in Free Energy Calculations with Grand Canonical Monte Carlo

2020 ◽  
Author(s):  
Gregory Ross ◽  
Ellery Russell ◽  
Yuqing Deng ◽  
Chao Lu ◽  
Edward Harder ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Free Energy ◽  
Drug Discovery ◽  
Free Energy Calculations ◽  
Data Sets ◽  
Grand Canonical Monte Carlo ◽  
Enhanced Sampling ◽  
Computational Performance ◽  
Energy Perturbation ◽  
Grand Canonical

<div>The prediction of protein-ligand binding affinities using free energy perturbation (FEP) is becoming increasingly routine in structure-based drug discovery. Most FEP packages use molecular dynamics (MD) to sample the configurations of proteins and ligands, as MD is well-suited to capturing coupled motion. However, MD can be prohibitively inefficient at sampling water molecules that are buried within binding sites, which has severely limited the domain of applicability of FEP and its prospective usage in drug discovery. In this paper, we present an advancement of FEP that augments MD with grand canonical Monte Carlo (GCMC), an enhanced sampling method, to overcome the problem of sampling water. We accomplished this without degrading computational performance. On both old and newly assembled data sets of proteinligand complexes, we show that the use of GCMC in FEP is essential for accurate and robust predictions for ligand perturbations that disrupt buried water. <br></div>

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