scholarly journals Molecular dynamics simulation of highly charged proteins: Comparison of the particle-particle particle-mesh and reaction field methods for the calculation of electrostatic interactions

2009 ◽  
Vol 12 (10) ◽  
pp. 2161-2172 ◽  
Author(s):  
Raimundo Gargallo ◽  
Philippe H. Hünenberger ◽  
Francesc X. Avilés ◽  
Baldomero Oliva
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Electrostatic Interactions ◽  
Dynamics Simulation ◽  
Field Methods ◽  
Reaction Field

scholarly journals Prediction of Drug Potencies of BACE1 Inhibitors: A Molecular Dynamics Simulation and MM_GB(PB)SA Scoring

2020 ◽  
Author(s):  
Mazen Hamed
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Electrostatic Interactions ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Energy Calculation ◽  
Brain Disorder ◽  
Kd Values

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder. One of the important therapeutic approaches of AD is the inhibition of β‐site APP cleaving enzyme‐1 (BACE1). This enzyme plays a central role in the synthesis of the pathogenic β-amyloid peptides (Aβ) in Alzheimer's disease. A group of potent BACE1 inhibitors with known x-ray structures (PDB ID 5i3X, 5i3Y, 5iE1, 5i3V, 5i3W, 4LC7, 3TPP) were studied by molecular dynamics simulation and binding energy calculation employing MM_GB(PB)SA. The calculated binding energies gave Kd values 0.139 µM, 1.39 nM, 4.39 mM, 24.3 nM, 1.39 mM, 29.13 mM and 193.07 nM, respectively. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. The Kd values were compared with experimental values, the structures were discussed in view of the energy contributions to binding. Drug likeness of these inhibitors is also discussed. Accommodation of ligands in the catalytic site of BACE1 is discussed depending on the type of fragment involved in each structure. Molecular dynamics (MD) simulations and energy studies were used to explore the recognition of the selected BACE1 inhibitors by Asp 32, Asp228 and the hydrophobic flap. The results show that selective BACE1 inhibition may be due to the formation of strong electrostatic interactions with Asp32 and Asp228 and a large number of hydrogen bonds, π-π and Van der Waals interactions with the amino acid residues located inside the catalytic cavity. Interactions with the ligands show a similar binding mode with BACE1. These results help to rationalize the design of selective BACE1 inhibitors.

scholarly journals Investigation of the Interaction of Drug Tetradecyltrimethylammonium Bromide with Cetyltrimethylammonium Bromide at Different Temperature

2020 ◽  
pp. 15-24
Author(s):  
Md. Matiar Rahman ◽  
Salina Rahman ◽  
Nasiruddin .
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Critical Micelle Concentration ◽  
Hydrophobic Interaction ◽  
Electrostatic Interactions ◽  
Cetyltrimethylammonium Bromide ◽  
Dynamics Simulation ◽  
Tetradecyltrimethylammonium Bromide ◽  
Transfer Energy ◽  
Mixed Systems

Antibiotic interaction between tetradecyltrimethylammonium bromide (TTAB) with cetyltrimethylammonium bromide (CTAB) has been studied in solution and within the attendance of salts at several temperatures (298.15, 303.15, 308.15, 313.15 and 318.15 K). One critical micelle concentration (CMC) was noted for pure CTAB and their mixture with the drug tetradecyltrimethylammonium bromide (TTAB). The CMC values for mixed systems (TTAB + CTAB) within the presence of salt exhibited lower in magnitude as compared to their absence. This acknowledged the first micellization of the mixture of TTAB and CTAB. All the G0m values were found to be negative for all systems. The H0m and S0m values disclosed that hydrophobic and electrostatic interactions were increased within the presence of salts compared to their absence at lower and better temperatures respectively. The opposite thermodynamics parameters like transfer energy (G0m.tr.), transfer enthalpy (H0m.tr.) also as transfer entropy (S0m.tr.) were also determined and discussed intimately. The inherent enthalpy gain (H0m) and therefore the compensation temperature (Tc) were also estimated and deliberated. Molecular dynamics simulation exposes that aqueous also as salt environment have an impact on the hydrophobic interaction between tetradecyltrimethylammonium bromide (TTAB) with cetyltrimethylammonium bromide (CTAB).

scholarly journals Prediction of Drug Potencies of BACE1 Inhibitors: A Molecular Dynamics Simulation and MM_GB(PB)SA Scoring

Computation ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 106
Author(s):  
Mazen Y. Hamed
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Electrostatic Interactions ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Energy Calculation ◽  
Brain Disorder ◽  
Kd Values

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder. One of the important therapeutic approaches of AD is the inhibition of β-site APP cleaving enzyme-1 (BACE1). This enzyme plays a central role in the synthesis of the pathogenic β-amyloid peptides (Aβ) in Alzheimer’s disease. A group of potent BACE1 inhibitors with known X-ray structures (PDB ID 5i3X, 5i3Y, 5iE1, 5i3V, 5i3W, 4LC7, 3TPP) were studied by molecular dynamics simulation and binding energy calculation employing MM_GB(PB)SA. The calculated binding energies gave Kd values of 0.139 µM, 1.39 nM, 4.39 mM, 24.3 nM, 1.39 mM, 29.13 mM, and 193.07 nM, respectively. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. The Kd values are compared with experimental values and the structures are discussed in view of the energy contributions to binding. Drug likeness of these inhibitors is also discussed. Accommodation of ligands in the catalytic site of BACE1 is discussed depending on the type of fragment involved in each structure. Molecular dynamics (MD) simulations and energy studies were used to explore the recognition of the selected BACE1 inhibitors by Asp32, Asp228, and the hydrophobic flap. The results show that selective BACE1 inhibition may be due to the formation of strong electrostatic interactions with Asp32 and Asp228 and a large number of hydrogen bonds, in addition to π–π and van der Waals interactions with the amino acid residues located inside the catalytic cavity. Interactions with the ligands show a similar binding mode with BACE1. These results help to rationalize the design of selective BACE1 inhibitors.

Handling Electrostatic Interactions in Molecular Simulations: A Systematic Study

2008 ◽  
Vol 73 (4) ◽  
pp. 481-506 ◽  
Author(s):  
Jiří Kolafa ◽  
Filip Moučka ◽  
Ivo Nezbeda
Keyword(s):  
Molecular Dynamics ◽  
Monte Carlo ◽  
Long Range ◽  
Electrostatic Interactions ◽  
Short Range ◽  
Ewald Summation ◽  
Field Methods ◽  
Reaction Field ◽  
Lennard Jones ◽  
Dynamics Simulations

Two qualitatively different models with strong long-range electrostatic interactions, Lennard-Jones diatomics with an embedded dipole moment and TIP4P/2005 water, are considered in extensive Monte Carlo and molecular dynamics simulations to systematically study the differences in results caused by different treatments of the long-range electrostatic interactions. In addition to the standard Ewald summation and reaction field methods, we consider also two variants of short-range approximations. Both thermodynamic and structural properties, and both homogeneous and inhomogeneous phases are considered. It is shown that the accuracy of the short-range approximations with carefully selected parameters may be sufficient for a number of applications; however, in some cases one can encounter accuracy limits or structural or other artifacts.

scholarly journals Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study

2019 ◽  
Author(s):  
Zana Pirkhezranian ◽  
Mojtaba Tahmurespur ◽  
Xavier Daura ◽  
Hassan Monhemi ◽  
Mohammadhadi Sekhavati
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Antimicrobial Peptides ◽  
Electrostatic Interactions ◽  
Binding Free Energy ◽  
Dna Interaction ◽  
Dynamics Simulation ◽  
Energy Estimates ◽  
Intracellular Target ◽  
Functional Relevance

Abstract Background: Lactoferrampin (LFampin), Lactoferricin (LFcin), and LFchimera are three well-known antimicrobial peptides derived from Lactoferrin and proposed as alternatives for antibiotics. Although the intracellular activity of these peptides has been previously demonstrated, their mode of action is not yet fully understood. Here, we performed a molecular dynamics simulation study to understand the molecular interactions between camel Lactoferrin derived peptides, including CLFampin, CLFcin, and CLFchimera, and DNA as an important intracellular target. Results: Our results indicate that all three peptides bind to DNA, albeit with different propensities, with CLFchimera showing the highest binding affinity. The secondary structures of the peptides, modeled on Lactoferrin, did not undergo significant changes during simulation, supporting their functional relevance. Main residues involved in the peptide-DNA interaction were identified based on binding free energy estimates calculated over 200 ns, which, as expected, confirmed strong electrostatic interactions between DNA phosphate groups and positively charged peptide side chains. Interaction between the different concentrations of CLFchimera and DNA revealed that after binding of four copies of CLFchimera to DNA, hydrogen bonds between the two strands of DNA start to break from one of the termini. Conclusions: Importantly, our results revealed that there is no DNA-sequence preference for peptide binding, in line with a broad antimicrobial activity. Moreover, the results showed that the strength of the interaction between DNA and CLFchimera is concentration dependent. The insight provided by these results can be used for the rational redesign of natural antimicrobial peptides targeting the bacterial DNA. Keywords: Keywords: Camel, Antimicrobial peptide, DNA, Lactoferrin, Molecular dynamics simulation

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