scholarly journals Human IgG1 Fc pH-dependent optimization from a constant pH molecular dynamics simulation analysis

RSC Advances ◽  
2020 ◽  
Vol 10 (22) ◽  
pp. 13066-13075
Author(s):  
Yee Ying Lim ◽  
Theam Soon Lim ◽  
Yee Siew Choong
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
In Silico ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Constant Ph ◽  
Human Igg1 ◽  
Ph Dependent ◽  
Constant Ph Molecular Dynamics

An in silico IgG-Fc variant with better affinity at pH 6.0 but retained the dissociation at pH 7.5 was designed.

scholarly journals pKa Determination of Histidine Residues in α-Conotoxin MII Peptides by 1H NMR and Constant pH Molecular Dynamics Simulation

2013 ◽  
Vol 117 (9) ◽  
pp. 2653-2661 ◽  
Author(s):  
Owen M. McDougal ◽  
David M. Granum ◽  
Mark Swartz ◽  
Conrad Rohleder ◽  
C. Mark Maupin
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
1H Nmr ◽  
Dynamics Simulation ◽  
Histidine Residues ◽  
Constant Ph ◽  
Pka Determination ◽  
Constant Ph Molecular Dynamics

scholarly journals Anti-TNF Alpha Antibody Humira with pH-dependent Binding Characteristics: A constant-pH Molecular Dynamics, Gaussian Accelerated Molecular Dynamics, and In Vitro Study

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 334
Author(s):  
Shih-Ting Hong ◽  
Yu-Cheng Su ◽  
Yu-Jen Wang ◽  
Tian-Lu Cheng ◽  
Yeng-Tseng Wang
Keyword(s):  
Molecular Dynamics ◽  
Tnf Alpha ◽  
Complex Structures ◽  
Binding Characteristics ◽  
Accelerated Molecular Dynamics ◽  
Constant Ph ◽  
Ph Dependent ◽  
Constant Ph Molecular Dynamics ◽  
Antibody Drug

Humira is a monoclonal antibody that binds to TNF alpha, inactivates TNF alpha receptors, and inhibits inflammation. Neonatal Fc receptors can mediate the transcytosis of Humira–TNF alpha complex structures and process them toward degradation pathways, which reduces the therapeutic effect of Humira. Allowing the Humira–TNF alpha complex structures to dissociate to Humira and soluble TNF alpha in the early endosome to enable Humira recycling is crucial. We used the cytoplasmic pH (7.4), the early endosomal pH (6.0), and pKa of histidine side chains (6.0–6.4) to mutate the residues of complementarity-determining regions with histidine. Our engineered Humira (W1-Humira) can bind to TNF alpha in plasma at neutral pH and dissociate from the TNF alpha in the endosome at acidic pH. We used the constant-pH molecular dynamics, Gaussian accelerated molecular dynamics, two-dimensional potential mean force profiles, and in vitro methods to investigate the characteristics of W1-Humira. Our results revealed that the proposed Humira can bind TNF alpha with pH-dependent affinity in vitro. The W1-Humira was weaker than wild-type Humira at neutral pH in vitro, and our prediction results were close to the in vitro results. Furthermore, our approach displayed a high accuracy in antibody pH-dependent binding characteristics prediction, which may facilitate antibody drug design. Advancements in computational methods and computing power may further aid in addressing the challenges in antibody drug design.

Molecular dynamics simulation analysis of conessine against multi drug resistant Serratia marcescens

2019 ◽  
Vol 67 ◽  
pp. 101-111
Author(s):  
Kalyani Dhusia ◽  
Kalpana Raja ◽  
Pierre Paul Michel Thomas ◽  
Pramod K. Yadav ◽  
Pramod W. Ramteke
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Serratia Marcescens ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Drug Resistant

scholarly journals pH-Dependent cooperativity and existence of a dry molten globule in the folding of a miniprotein BBL

2018 ◽  
Vol 20 (5) ◽  
pp. 3523-3530 ◽  
Author(s):  
Zhi Yue ◽  
Jana Shen
Keyword(s):  
Molecular Dynamics ◽  
Energy Barrier ◽  
Molten Globule ◽  
Free Energy Barrier ◽  
Molten Globule State ◽  
Constant Ph ◽  
Ph Dependent ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics ◽  
Folding Free Energy

Constant pH molecular dynamics simulations of BBL reveals negligible folding free energy barrier that is pH dependent and a sparsely populated dry molten globule state.

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