Pembuatan Protokol Penapisan Virtual Berbasis Stuktur (pvbs) untuk Identifikasi Ligan Inhibitor Reseptor Platelet-Activating Factor (PAF-r) sebagai Target Terapeutik Asma menggunakan YASARA

Platelet-activating factor receptors (PAF-r) is known as one of the receptors that affect asthma, while the Y-21480 ligand is reported as an effective, specific, and active PAF-r antagonist for asthma patients. Research in building structure-based virtual screening protocol (SBVS) for identification of PAF-r ligand inhibitors has been performed, the receptor crystal structure was obtained from the Protein Data Bank (PDB ID: 5zkp), while the ligand used as a leading compound is Y-24180, obtained from U.S. National Library of Medicine. Interactions between ligands and receptors are observed through molecular dynamics simulations using the YASARA program at intervals up to 20 nanoseconds, ligand-receptor binding stability occurs after a time interval of 2 nanoseconds, the lowest ligand-receptor binding energy occurs at a time interval of 1,401 picoseconds. Internal validation by re-docking 1,000 times the ligand to receptor resulted in a value of Root Mean Square Deviation (RMSD) of 0.6037 Å, confirmed that SBVS protocol was accurately able to reproduce the Y-24180 ligand pose on the 5zkp crystal structure, the protocol can be used as a new approach for investigation or design of compounds that have therapeutic potential as anti-asthma.

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Parameterization of Divalent Cations for Coarse-Grained Simulations

10.26434/chemrxiv.11881716 ◽

2020 ◽

Author(s):

Florencia Klein ◽

Daniela Cáceres-Rojas ◽

Monica Carrasco ◽

Juan Carlos Tapia ◽

Julio Caballero ◽

...

Keyword(s):

Molecular Dynamics ◽

Metal Ions ◽

Molecular Dynamics Simulations ◽

Divalent Cations ◽

Computational Cost ◽

Data Bank ◽

Coarse Grained ◽

Interaction Parameters ◽

Dynamics Simulations ◽

Dynamical Description

<p>Although molecular dynamics simulations allow for the study of interactions among virtually all biomolecular entities, metal ions still pose significant challenges to achieve an accurate structural and dynamical description of many biological assemblies. This is particularly the case for coarse-grained (CG) models. Although the reduced computational cost of CG methods often makes them the technique of choice for the study of large biomolecular systems, the parameterization of metal ions is still very crude or simply not available for the vast majority of CG- force fields. Here, we show that incorporating statistical data retrieved from the Protein Data Bank (PDB) to set specific Lennard-Jones interactions can produce structurally accurate CG molecular dynamics simulations. Using this simple approach, we provide a set of interaction parameters for Calcium, Magnesium, and Zinc ions, which cover more than 80% of the metal-bound structures reported on the PDB. Simulations performed using the SIRAH force field on several proteins and DNA systems show that using the present approach it is possible to obtain non-bonded interaction parameters that obviate the use of topological constraints. </p>

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Combined Use of Structure Analysis, Studies of Molecular Association in Solution, and Molecular Modelling to Understand the Different Propensities of Dihydroxybenzoic Acids to Form Solid Phases

Pharmaceutics ◽

10.3390/pharmaceutics13050734 ◽

2021 ◽

Vol 13 (5) ◽

pp. 734

Author(s):

Aija Trimdale ◽

Anatoly Mishnev ◽

Agris Bērziņš

Keyword(s):

Crystal Structure ◽

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Structure Analysis ◽

Crystal Structure Analysis ◽

Molecular Association ◽

Hydroxyl Groups ◽

Solid Phases ◽

Solvent Molecules ◽

Dynamics Simulations

The arrangement of hydroxyl groups in the benzene ring has a significant effect on the propensity of dihydroxybenzoic acids (diOHBAs) to form different solid phases when crystallized from solution. All six diOHBAs were categorized into distinctive groups according to the solid phases obtained when crystallized from selected solvents. A combined study using crystal structure and molecule electrostatic potential surface analysis, as well as an exploration of molecular association in solution using spectroscopic methods and molecular dynamics simulations were used to determine the possible mechanism of how the location of the phenolic hydroxyl groups affect the diversity of solid phases formed by the diOHBAs. The crystal structure analysis showed that classical carboxylic acid homodimers and ring-like hydrogen bond motifs consisting of six diOHBA molecules are prominently present in almost all analyzed crystal structures. Both experimental spectroscopic investigations and molecular dynamics simulations indicated that the extent of intramolecular bonding between carboxyl and hydroxyl groups in solution has the most significant impact on the solid phases formed by the diOHBAs. Additionally, the extent of hydrogen bonding with solvent molecules and the mean lifetime of solute–solvent associates formed by diOHBAs and 2-propanol were also investigated.

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WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

Journal of Theoretical and Computational Chemistry ◽

10.1142/s0219633613410022 ◽

2013 ◽

Vol 12 (08) ◽

pp. 1341002 ◽

Cited By ~ 1

Author(s):

XIN ZHANG ◽

MING LEI

Keyword(s):

Crystal Structure ◽

Molecular Dynamics ◽

Hydrogen Bonds ◽

Proton Transfer ◽

Glutamic Acid ◽

Active Site ◽

Nucleophilic Attack ◽

Zinc Ions ◽

Initial Model ◽

Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

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The crystal structure and molecular conformation of threo 5-methylmetadone in relation to opioid receptor binding

Tetrahedron ◽

10.1016/0040-4020(84)85051-6 ◽

1984 ◽

Vol 40 (3) ◽

pp. 467-471 ◽

Cited By ~ 6

Author(s):

W.L. Duax ◽

G.D. Smith ◽

J.F. Griffin ◽

P.D. Strong ◽

P.S. Portoghese

Keyword(s):

Crystal Structure ◽

Opioid Receptor ◽

Receptor Binding ◽

Molecular Conformation ◽

Opioid Receptor Binding

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Crystal structure of the wild-type and D30A mutant thioredoxin h of Chlamydomonas reinhardtii and implications for the catalytic mechanism

Biochemical Journal ◽

10.1042/bj3590065 ◽

2001 ◽

Vol 359 (1) ◽

pp. 65-75 ◽

Cited By ~ 25

Author(s):

Valeria MENCHISE ◽

Catherine CORBIER ◽

Claude DIDIERJEAN ◽

Michele SAVIANO ◽

Ettore BENEDETTI ◽

...

Keyword(s):

Crystal Structure ◽

Proton Transfer ◽

Chlamydomonas Reinhardtii ◽

Catalytic Mechanism ◽

Structural Data ◽

Careful Analysis ◽

Wild Type ◽

Thioredoxin H ◽

Dynamics Simulations

Thioredoxins are ubiquitous proteins which catalyse the reduction of disulphide bridges on target proteins. The catalytic mechanism proceeds via a mixed disulphide intermediate whose breakdown should be enhanced by the involvement of a conserved buried residue, Asp-30, as a base catalyst towards residue Cys-39. We report here the crystal structure of wild-type and D30A mutant thioredoxin h from Chlamydomonas reinhardtii, which constitutes the first crystal structure of a cytosolic thioredoxin isolated from a eukaryotic plant organism. The role of residue Asp-30 in catalysis has been revisited since the distance between the carboxylate OD1 of Asp-30 and the sulphur SG of Cys-39 is too great to support the hypothesis of direct proton transfer. A careful analysis of all available crystal structures reveals that the relative positioning of residues Asp-30 and Cys-39 as well as hydrophobic contacts in the vicinity of residue Asp-30 do not allow a conformational change sufficient to bring the two residues close enough for a direct proton transfer. This suggests that protonation/deprotonation of Cys-39 should be mediated by a water molecule. Molecular-dynamics simulations, carried out either in vacuo or in water, as well as proton-inventory experiments, support this hypothesis. The results are discussed with respect to biochemical and structural data.

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Crystal Structure of Thaumatin I, a Sweet Taste Receptor Binding Protein

Crystallography in Molecular Biology ◽

10.1007/978-1-4684-5272-3_36 ◽

1987 ◽

pp. 395-402

Author(s):

Abraham de Vos ◽

Sung-Hou Kim

Keyword(s):

Crystal Structure ◽

Receptor Binding ◽

Binding Protein ◽

Taste Receptor ◽

Sweet Taste ◽

Sweet Taste Receptor ◽

Receptor Binding Protein

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Crystal structure of the receptor-binding domain of human B7-2: Insights into organization and signaling

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.252771499 ◽

2003 ◽

Vol 100 (5) ◽

pp. 2586-2591 ◽

Cited By ~ 62

Author(s):

X. Zhang ◽

J.-C. D. Schwartz ◽

S. C. Almo ◽

S. G. Nathenson

Keyword(s):

Crystal Structure ◽

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain

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Residue-Residue Mutual Work Analysis of Retinal-Opsin Interaction in Rhodopsin: Implications for Protein-Ligand Binding

10.1101/711952 ◽

2019 ◽

Author(s):

Wenjin Li

Keyword(s):

Virtual Work ◽

Interaction Matrix ◽

Time Interval ◽

Transition Path ◽

Transition Path Sampling ◽

Decomposition Approach ◽

Work Analysis ◽

Nmr Study ◽

The Matrix ◽

Dynamics Simulations

AbstractEnergetic contributions at single-residue level to retinal-opsin interaction in rhodopsin were studied by combining molecular dynamics simulations, transition path sampling, and a newly developed energy decomposition approach. The virtual work at an infinitesimal time interval was decomposed into the work components on one residue due to its interaction with another residue, which were then averaged over the transition path ensemble along a proposed reaction coordinate. Such residue-residue mutual work analysis on 62 residues within the active center of rhodopsin resulted in a very sparse interaction matrix, which is generally not symmetric but anti-symmetric to some extent. 14 residues were identified to be major players in retinal relaxation, which is in excellent agreement with an existing NMR study. Based on the matrix of mutual work, a comprehensive network was constructed to provide detailed insights into the chromophore-protein interaction from a viewpoint of energy flow.

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