Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair

Nanoscale ◽  
2015 ◽  
Vol 7 (9) ◽  
pp. 3876-3887 ◽  
Author(s):  
D. Marson ◽  
E. Laurini ◽  
P. Posocco ◽  
M. Fermeglia ◽  
S. Pricl
Keyword(s):  
Free Energy ◽  
Gene Delivery ◽  
Molecular Simulations ◽  
Molecular Parameter ◽  
Carbosilane Dendrimers ◽  
Free Energy Of Binding ◽  
Oligonucleotide Binding

Molecular simulations individuate the normalized effective free energy of binding as a critical molecular parameter in designing efficient nanovectors for gene delivery.

Development of Xanthine Based Inhibitors Targeting Phosphodiesterase 9A

2017 ◽  
Vol 14 (10) ◽  
pp. 1122-1137 ◽  
Author(s):  
Nivedita Singh ◽  
Parameswaran Saravanan ◽  
M.S. Thakur ◽  
Sanjukta Patra
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Signal Transduction Pathway ◽  
Docking Study ◽  
Primary Objective ◽  
Cgmp Level ◽  
Active Site Residues ◽  
Aromatic Fragment ◽  
Docking Approach ◽  
Free Energy Of Binding

Background: Phosphodiesterases 9A (PDE9A) is one of the prominent regulating enzymes of the signal transduction pathway having highest catalytic affinity for second messenger, cGMP. When the cGMP level is lowered, an uncontrolled expression of PDE9A may lead to various neurodegenerative diseases. To regulate the catalytic activity of PDE9A, potent inhibitors are needed. Objective: The primary objective of the present study was to develop new xanthine based inhibitors targeting PDE9A. This study was an attempt to bring structural diversification in PDE9A inhibitor development because most of the existing inhibitors are constructed over pyrazolopyrimidinone scaffold. Methods: Manual designing and parallel molecular docking approach were used for the development of xanthine derivatives. In this study, N1, N3, N9 and C8 positions of xanthine scaffold were selected as substitution sites to design 200 new compounds. Reverse docking and pharmaceutical analyses were used for final validation of most promising compounds. Results: By keeping free energy of binding cut-off of -6.0 kcal/mol, 52 compounds were screened. The compounds with substitution at N1, N3 and C8 positions of xanthine showed good occupancy in PDE9A active site pocket with a significant interaction pattern. This was further validated by screening different factors such as free energy of binding, inhibition constant and interacting active site residues in the 5Å region. Substitution at C8 position with phenyl substituent determined the inhibition affinity of compounds towards PDE9A by establishing a strong hydrophobic - hydrophobic interaction. The alkyl chain at N1 position generated selectivity of compounds towards PDE9A. The aromatic fragment at N3 position increased the binding affinity of compounds. Thus, by comparative docking study, it was found that compound 39-42 formed selective interaction towards PDE9A over other members of the PDE superfamily. Conclusion: From the present study, N1, N3 and C8 positions of xanthine were concluded as the best sites for substitution for the generation of potent PDE9A inhibitors.

Free energy of conformational change in a single chain of polyvinylidene fluoride using molecular simulations

2021 ◽  
Vol 61 (4) ◽  
pp. 1270-1280
Author(s):  
Shubham Mireja ◽  
Devang V. Khakhar
Keyword(s):  
Free Energy ◽  
Conformational Change ◽  
Polyvinylidene Fluoride ◽  
Molecular Simulations ◽  
Single Chain

scholarly journals How proteins open fusion pores: insights from molecular simulations

2020 ◽  
Author(s):  
H. Jelger Risselada ◽  
Helmut Grubmüller
Keyword(s):  
Free Energy ◽  
Fusion Proteins ◽  
Graphics Processing Units ◽  
Fusion Reaction ◽  
Molecular Simulations ◽  
Minimum Free Energy ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Fusion Pore ◽  
Graphics Processing

AbstractFusion proteins can play a versatile and involved role during all stages of the fusion reaction. Their roles go far beyond forcing the opposing membranes into close proximity to drive stalk formation and fusion. Molecular simulations have played a central role in providing a molecular understanding of how fusion proteins actively overcome the free energy barriers of the fusion reaction up to the expansion of the fusion pore. Unexpectedly, molecular simulations have revealed a preference of the biological fusion reaction to proceed through asymmetric pathways resulting in the formation of, e.g., a stalk-hole complex, rim-pore, or vertex pore. Force-field based molecular simulations are now able to directly resolve the minimum free-energy path in protein-mediated fusion as well as quantifying the free energies of formed reaction intermediates. Ongoing developments in Graphics Processing Units (GPUs), free energy calculations, and coarse-grained force-fields will soon gain additional insights into the diverse roles of fusion proteins.

scholarly journals Relative free energy of binding between antimicrobial peptides and SDS or DPC micelles

2009 ◽  
Vol 35 (10-11) ◽  
pp. 986-997 ◽  
Author(s):  
Abdallah Sayyed-Ahmad ◽  
Himanshu Khandelia ◽  
Yiannis N. Kaznessis
Keyword(s):  
Free Energy ◽  
Antimicrobial Peptides ◽  
Relative Free Energy ◽  
Free Energy Of Binding

scholarly journals Accurate calculation of the absolute free energy of binding for drug molecules

2016 ◽  
Vol 7 (1) ◽  
pp. 207-218 ◽  
Author(s):  
Matteo Aldeghi ◽  
Alexander Heifetz ◽  
Michael J. Bodkin ◽  
Stefan Knapp ◽  
Philip C. Biggin
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Free Energy Calculations ◽  
Accurate Calculation ◽  
Energy Calculations ◽  
Thermodynamic Cycles ◽  
Drug Molecules ◽  
The Absolute ◽  
Free Energy Of Binding

Free energy calculations based on molecular dynamics and thermodynamic cycles accurately reproduce experimental affinities of diverse bromodomain inhibitors.

scholarly journals Free Energy of Binding of Coiled-Coil Complexes with Different Electrostatic Environments: The Influence of Force Field Polarisation and Capping

2014 ◽  
Vol 4 (5) ◽  
pp. 285-295 ◽  
Author(s):  
Zhi-Li Zuo ◽  
Ling Guo ◽  
Ricardo L. Mancera
Keyword(s):  
Free Energy ◽  
Force Field ◽  
Coiled Coil ◽  
Free Energy Of Binding
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