Molecular Dynamics Studies on the Bacterial Membrane Pore Formation by Small Molecule Antimicrobial Agents

2021 ◽  
Author(s):  
Felsis Angelene Daison ◽  
Nitheeshkumar Kumar ◽  
Siranjeevi Balakrishnan ◽  
Kavyashree Venugopal ◽  
Sangamithra Elango ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Small Molecule ◽  
Pore Formation ◽  
Antimicrobial Agents ◽  
Bacterial Membrane ◽  
Membrane Pore

scholarly journals Evaluation of the Binding Mechanism of Human Defensin 5 in a Bacterial Membrane: A Simulation Study

2021 ◽  
Vol 22 (22) ◽  
pp. 12401
Author(s):  
Tadsanee Awang ◽  
Phoom Chairatana ◽  
Ranjit Vijayan ◽  
Prapasiri Pongprayoon
Keyword(s):  
Molecular Dynamics ◽  
Host Defense ◽  
Pore Formation ◽  
Md Simulations ◽  
Bacterial Membrane ◽  
Binding Mechanism ◽  
Gram Negative ◽  
Host Defense Peptide ◽  
Human Defensin 5 ◽  
Binding Mechanisms

Human α-defensin 5 (HD5) is a host-defense peptide exhibiting broad-spectrum antimicrobial activity. The lipopolysaccharide (LPS) layer on the Gram-negative bacterial membrane acts as a barrier to HD5 insertion. Therefore, the pore formation and binding mechanism remain unclear. Here, the binding mechanisms at five positions along the bacterial membrane axis were investigated using Molecular Dynamics. (MD) simulations. We found that HD5 initially placed at positions 1 to 3 moved up to the surface, while HD5 positioned at 4 and 5 remained within the membrane interacting with the middle and inner leaflet of the membrane, respectively. The arginines were key components for tighter binding with 3-deoxy-d-manno-octulosonic acid (KDO), phosphates of the outer and inner leaflets. KDO appeared to retard the HD5 penetration.

Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach

2018 ◽  
Author(s):  
Benjamin R. Jagger ◽  
Christoper T. Lee ◽  
Rommie Amaro
Keyword(s):  
Molecular Dynamics ◽  
Drug Discovery ◽  
Small Molecule ◽  
Brownian Dynamics ◽  
Model Simulation ◽  
Computational Cost ◽  
Lead Selection ◽  
Delta G ◽  
Dynamics Simulations

<p>The ranking of small molecule binders by their kinetic (kon and koff) and thermodynamic (delta G) properties can be a valuable metric for lead selection and optimization in a drug discovery campaign, as these quantities are often indicators of in vivo efficacy. Efficient and accurate predictions of these quantities can aid the in drug discovery effort, acting as a screening step. We have previously described a hybrid molecular dynamics, Brownian dynamics, and milestoning model, Simulation Enabled Estimation of Kinetic Rates (SEEKR), that can predict kon’s, koff’s, and G’s. Here we demonstrate the effectiveness of this approach for ranking a series of seven small molecule compounds for the model system, -cyclodextrin, based on predicted kon’s and koff’s. We compare our results using SEEKR to experimentally determined rates as well as rates calculated using long-timescale molecular dynamics simulations and show that SEEKR can effectively rank the compounds by koff and G with reduced computational cost. We also provide a discussion of convergence properties and sensitivities of calculations with SEEKR to establish “best practices” for its future use.</p>

scholarly journals Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers

Soft Matter ◽  
2021 ◽  
Author(s):  
Garima Rani ◽  
Kenichi Kuroda ◽  
Satyavani Vemparala
Keyword(s):  
Molecular Dynamics ◽  
Antimicrobial Peptide ◽  
Bacterial Membrane ◽  
Simulation Data ◽  
Antimicrobial Polymers ◽  
Polar Groups ◽  
Methacrylate Polymers ◽  
Dynamics Simulations ◽  
Polar Functional Groups

Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows...

Membrane pore formation at protein–lipid interfaces

2014 ◽  
Vol 39 (11) ◽  
pp. 510-516 ◽  
Author(s):  
Robert J.C. Gilbert ◽  
Mauro Dalla Serra ◽  
Christopher J. Froelich ◽  
Mark I. Wallace ◽  
Gregor Anderluh
Keyword(s):  
Pore Formation ◽  
Membrane Pore

scholarly journals Molecular Basis for Membrane Pore Formation by Bax Protein Carboxyl Terminus

Biochemistry ◽  
2012 ◽  
Vol 51 (46) ◽  
pp. 9406-9419 ◽  
Author(s):  
Suren A. Tatulian ◽  
Pranav Garg ◽  
Kathleen N. Nemec ◽  
Bo Chen ◽  
Annette R. Khaled
Keyword(s):  
Molecular Basis ◽  
Pore Formation ◽  
Carboxyl Terminus ◽  
Membrane Pore ◽  
Bax Protein

Machine learning and molecular dynamics simulations assisted evolutionary design and discovery pipeline to screen the efficient small molecule acceptors for PTB7-Th based organic solar cells with over 15% efficiency

2022 ◽  
Author(s):  
Jin-Liang Wang ◽  
Asif Mahmood ◽  
Ahmad Irfan
Keyword(s):  
Machine Learning ◽  
Molecular Dynamics ◽  
Solar Cells ◽  
Molecular Dynamics Simulations ◽  
Small Molecule ◽  
Organic Solar Cells ◽  
Evolutionary Design ◽  
New Materials ◽  
Dynamics Simulations ◽  
Discovery Pipeline

Organic solar cells are the most promising candidates for future commercialization. This goal can be quickly achieved by designing new materials and predicting their performance without experimentation to reduce the...

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