The Origin of the Method of Steepest Descent

Petrova, S. S.; Solov'ev, A D

doi:10.1006/hmat.1996.2146

Cited by 134 publications

(79 citation statements)

References 3 publications

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“…[8] For the removal of initial steric clashes, 5000-steps energy minimization is performed for each system using the steepest descent method. [41] Subsequently, a 200 ps equilibration in NVT ensemble is performed to equilibrate each system at 310 K and to avoid any kind of void formation in the box followed by a 5 ns equilibration at isothermal-isobaric (NPT) ensemble to attain a steady pressure of 1 atm. This period of equilibration is found to be sufficient enough for the convergence of properties like pressure, temperature for each system.…”

Section: Simulation Detailsmentioning

confidence: 99%

Choline Chloride as a Nano‐Crowder Protects HP‐36 from Urea‐Induced Denaturation: Insights from Solvent Dynamics and Protein‐Solvent Interactions

et al. 2020

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Urea at sufficiently high concentration unfolds the secondary structure of proteins leading to denaturation. In contrast, choline chloride (ChCl) and urea, in 1 : 2 molar ratio, form a deep eutectic mixture, a liquid at room temperature, protecting proteins from denaturation. In order to get a microscopic picture of this phenomenon, we perform extensive all‐atom molecular dynamics simulations on a model protein, HP‐36. Based on our calculation of Kirkwood‐Buff integrals, we analyze the relative accumulation of urea and ChCl around the protein. Additional insights are drawn from the translational and rotational dynamics of solvent molecules and hydrogen bond auto‐correlation functions. In the presence of urea, water shows slow subdiffusive dynamics around the protein owing to a strong interaction of water with the backbone atoms. Urea also shows subdiffusive motion. The addition of ChCl further slows down the dynamics of urea, restricting its accumulation around the protein backbone. Adding to this, choline cations in the first solvation shell of the protein show the strongest subdiffusive behavior. In other words, ChCl acts as a nano‐crowder by excluding urea from the protein backbone and thereby slowing down the dynamics of water around the protein. This prevents the protein from denaturation and makes it structurally rigid, which is supported by the smaller radius of gyration and root mean square deviation values of HP‐36.

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Section: Simulation Detailsmentioning

confidence: 99%

Choline Chloride as a Nano‐Crowder Protects HP‐36 from Urea‐Induced Denaturation: Insights from Solvent Dynamics and Protein‐Solvent Interactions

et al. 2020

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“…[22] Before MD simulations, the complexes were gradually relaxed using 10 000 cycles of minimization (500 cycles of steepest descent [23,24] and 9500 cycles of conjugate gradient minimization [25] ). The general CHARMM36 force was used to generate the force field parameters for protein and ligands.…”

Section: Computational Studiesmentioning

confidence: 99%

Virtual Pharmacophore Screening Identifies Small‐Molecule Inhibitors of the Rev1‐CT/RIR Protein–Protein Interaction

et al. 2019

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Translesion synthesis (TLS) has emerged as a mechanism through which several forms of cancer develop acquired resistance to first‐line genotoxic chemotherapies by allowing replication to continue in the presence of damaged DNA. Small molecules that inhibit TLS hold promise as a novel class of anticancer agents that can serve to enhance the efficacy of these front‐line therapies. We previously used a structure‐based rational design approach to identify the phenazopyridine scaffold as an inhibitor of TLS that functions by disrupting the protein–protein interaction (PPI) between the C‐terminal domain of the TLS DNA polymerase Rev1 (Rev1‐CT) and the Rev1 interacting regions (RIR) of other TLS DNA polymerases. To continue the identification of small molecules that disrupt the Rev1‐CT/RIR PPI, we generated a pharmacophore model based on the phenazopyridine scaffold and used it in a structure‐based virtual screen. In vitro analysis of promising hits identified several new chemotypes with the ability to disrupt this key TLS PPI. In addition, several of these compounds were found to enhance the efficacy of cisplatin in cultured cells, highlighting their anti‐TLS potential.

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“…A constant temperature and pressure for the whole system (300 K and 1 bar) was achieved with the Berendsen thermostat [25] and the Parrinello and Rahman [26] barostat parameters. Steepest descent energy minimization process [27] was utilized to minimize the simulated system step-by-step until a tolerance of 1000 kJ/mol was achieved. A pH of 7 was maintained for all the molecular dynamics simulation processes.…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Role of Hydrophobic Patch in LRP6: A Promising Drug Target for Alzheimer's disease

Muthusamy¹,

Prasad²

2016

ijps

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Muthusamy, et al.: Hydrophobic Patch in LRP6 for Alzheimer's disease Alzheimer's disease is one of the most fatal dementia occurring in elderly persons. LRP6 and DKK1 proteins are found in the senile plaques of Alzheimer's disease patients. Inducing the disassociation/inhibition of the LRP6-DKK1 complex is a vital mechanism for the treatment of Alzheimer's disease. This study accomplished its goal of targeting potent inhibitors against LRP6 by molecular modeling techniques such as high throughput virtual screening and molecular dynamics simulations. Zinc database compounds were docked in the hydrophobic patch of LRP6 and in the active site of DKK1 using the GLIDE module. The initial docking results were well exemplified to amino acid residues interacting on the hydrophobic patch of LRP6 and active sites of DKK1. Further, the best hit compounds (866) were again redocked with Glide XP and finally six lead compounds were identified as the best inhibitors against LRP6 which was later confirmed by molecular dynamics simulation studies.

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The Origin of the Method of Steepest Descent

Cited by 134 publications

References 3 publications

Choline Chloride as a Nano‐Crowder Protects HP‐36 from Urea‐Induced Denaturation: Insights from Solvent Dynamics and Protein‐Solvent Interactions

Choline Chloride as a Nano‐Crowder Protects HP‐36 from Urea‐Induced Denaturation: Insights from Solvent Dynamics and Protein‐Solvent Interactions

Virtual Pharmacophore Screening Identifies Small‐Molecule Inhibitors of the Rev1‐CT/RIR Protein–Protein Interaction

Role of Hydrophobic Patch in LRP6: A Promising Drug Target for Alzheimer's disease

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