scholarly journals Predicting Immunogenicity Risk in Biopharmaceuticals

Symmetry ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 388
Author(s):  
Nikolet Doneva ◽  
Irini Doytchinova ◽  
Ivan Dimitrov
Keyword(s):  
Machine Learning Algorithms ◽  
Computational Tools ◽  
Binding Motifs ◽  
B Cell Epitopes ◽  
Crucial Step ◽  
Histocompatibility Complex ◽  
Alignment Algorithms ◽  
Experimental Approaches ◽  
Dynamics Simulations ◽  
Allergenicity Prediction

The assessment of immunogenicity of biopharmaceuticals is a crucial step in the process of their development. Immunogenicity is related to the activation of adaptive immunity. The complexity of the immune system manifests through numerous different mechanisms, which allows the use of different approaches for predicting the immunogenicity of biopharmaceuticals. The direct experimental approaches are sometimes expensive and time consuming, or their results need to be confirmed. In this case, computational methods for immunogenicity prediction appear as an appropriate complement in the process of drug design. In this review, we analyze the use of various In silico methods and approaches for immunogenicity prediction of biomolecules: sequence alignment algorithms, predicting subcellular localization, searching for major histocompatibility complex (MHC) binding motifs, predicting T and B cell epitopes based on machine learning algorithms, molecular docking, and molecular dynamics simulations. Computational tools for antigenicity and allergenicity prediction also are considered.

scholarly journals MHC genes and oxidative stress in sticklebacks: an immuno-ecological approach

2006 ◽  
Vol 273 (1592) ◽  
pp. 1407-1414 ◽  
Author(s):  
Joachim Kurtz ◽  
K. Mathias Wegner ◽  
Martin Kalbe ◽  
Thorsten B.H Reusch ◽  
Helmut Schaschl ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Susceptibility To Infection ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Individual Host ◽  
Experimental Approaches ◽  
Mhc Class Iib ◽  
Class Iib ◽  
First Time ◽  
And Oxidative Stress

Individual variation in the susceptibility to infection may result from the varying ability of hosts to specifically recognize different parasite strains. Alternatively, there could be individual host differences in fitness costs of immune defence. Although, these two explanations are not mutually exclusive, they have so far been treated in separate experimental approaches. To analyse potential relationships, we studied body condition and oxidative stress, which may reflect costs of immunity, in three-spined sticklebacks that had been experimentally exposed to three species of naturally occurring parasite. These sticklebacks differed in a trait, which is crucial to specific parasite defence, i.e. individual genetic diversity at major histocompatibility complex (MHC) class IIB loci. Oxidative stress was quantified as tissue acrolein, a technique that has been applied to questions of immuno-ecology for the first time. We measured gene expression at the MHC and other estimates of immune activation. We found that fish with high levels of MHC expression had poor condition and elevated oxidative stress. These results indicate that MHC-based specific immunity is connected with oxidative stress. They could, thus, also be relevant in the broader context of the evolution of sexually selected signals that are based on carotenoids and are, thus supposed to reflect oxidative stress resistance.

scholarly journals Optimization of Molecular Dynamics Simulations of c-MYC1-88—An Intrinsically Disordered System

Life ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 109 ◽  
Author(s):  
Sandra S. Sullivan ◽  
Robert O.J. Weinzierl
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Proliferation And Apoptosis ◽  
Conventional Structure ◽  
Experimental Approaches ◽  
Dynamics Simulations

Many of the proteins involved in key cellular regulatory events contain extensive intrinsically disordered regions that are not readily amenable to conventional structure/function dissection. The oncoprotein c-MYC plays a key role in controlling cell proliferation and apoptosis and more than 70% of the primary sequence is disordered. Computational approaches that shed light on the range of secondary and tertiary structural conformations therefore provide the only realistic chance to study such proteins. Here, we describe the results of several tests of force fields and water models employed in molecular dynamics simulations for the N-terminal 88 amino acids of c-MYC. Comparisons of the simulation data with experimental secondary structure assignments obtained by NMR establish a particular implicit solvation approach as highly congruent. The results provide insights into the structural dynamics of c-MYC1-88, which will be useful for guiding future experimental approaches. The protocols for trajectory analysis described here will be applicable for the analysis of a variety of computational simulations of intrinsically disordered proteins.

scholarly journals Navigating Traditional Chinese Medicine Network Pharmacology and Computational Tools

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Ming Yang ◽  
Jia-Lei Chen ◽  
Li-Wen Xu ◽  
Guang Ji
Keyword(s):  
Systems Biology ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Network Models ◽  
Research Process ◽  
Modern Medicine ◽  
Machine Learning Algorithms ◽  
Network Pharmacology ◽  
Research Approach ◽  
Computational Tools

The concept of “network target” has ushered in a new era in the field of traditional Chinese medicine (TCM). As a new research approach, network pharmacology is based on the analysis of network models and systems biology. Taking advantage of advancements in systems biology, a high degree of integration data analysis strategy and interpretable visualization provides deeper insights into the underlying mechanisms of TCM theories, including the principles of herb combination, biological foundations of herb or herbal formulae action, and molecular basis of TCM syndromes. In this study, we review several recent developments in TCM network pharmacology research and discuss their potential for bridging the gap between traditional and modern medicine. We briefly summarize the two main functional applications of TCM network models: understanding/uncovering and predicting/discovering. In particular, we focus on how TCM network pharmacology research is conducted and highlight different computational tools, such as network-based and machine learning algorithms, and sources that have been proposed and applied to the different steps involved in the research process. To make network pharmacology research commonplace, some basic network definitions and analysis methods are presented.

Elucidating the CO2 adsorption mechanisms in the triangular channels of the bis(pyrazolate) MOF Fe2(BPEB)3 by in situ synchrotron X-ray diffraction and molecular dynamics simulations

2017 ◽  
Vol 5 (32) ◽  
pp. 16964-16975 ◽  
Author(s):  
C. Giacobbe ◽  
E. Lavigna ◽  
A. Maspero ◽  
S. Galli
Keyword(s):  
Molecular Dynamics ◽  
Co2 Adsorption ◽  
Metal Organic Framework ◽  
X Ray Diffraction ◽  
Computational Tools ◽  
X Ray ◽  
Adsorption Mechanisms ◽  
Metal Organic ◽  
Dynamics Simulations

The structural origin of the remarkable performance of the metal–organic framework Fe2(BPEB)3 as a CO2 adsorbent (40.5% of the host weight at 298 K and 10 bar) was investigated by combining advanced experimental and computational tools.

scholarly journals The Binding of Phosphorus Species at Goethite: A Joint Experimental and Theoretical Study

2021 ◽  
Author(s):  
Prasanth B. Ganta ◽  
Mohsen Morshedizad ◽  
Oliver Kühn ◽  
Peter Leinweber ◽  
Ashour A. Ahmed
Keyword(s):  
Ab Initio Molecular Dynamics ◽  
Phosphorus Species ◽  
Binding Motifs ◽  
Freundlich Model ◽  
Soil P ◽  
Op Amp ◽  
Proton Transfers ◽  
Mineral Binding ◽  
Dynamics Simulations ◽  
Phosphate Groups

Knowledge of the interaction between inorganic and organic phosphates with soil minerals is vital for improving the soil P fertility. To achieve an in-depth understanding we combined adsorption experiments and hybrid ab initio molecular dynamics simulations to analyze the adsorption of common phosphates, i.e. orthophosphate (OP), glycerolphosphate (GP) and inositolhexaphosphate (IHP), onto the 100 surface plane of goethite. Experimental adsorption data per mol P-molecule basis fitted to the Freundlich model show the adsorption strength increases in the order GP < OP < IHP, and IHP adsorption being saturated faster followed by GP and OP. Modeling results show that OP and GP form stable monodentate (M) and binuclear bidentate (B) motifs with B being more stable than M, whereas IHP forms stable M and 3M motifs. Interfacial water plays an important role through hydrogen bonds and proton transfers with OP/GP/IHP and goethite. It also controls the binding motifs of phosphates with goethite. Combining both experimental and modeling results, we propose that the B motif dominates for OP, whereas GP forms M and IHP forms a combination of M and 3M motifs. The joint approach plausibly explains why IHP is the predominant organically bound P form in soil. This study could be considered as a preliminary step for further studies for understanding the mechanisms of how microbes and plants overcome the strong IHP–mineral binding to implement the phosphate groups into their metabolism.

scholarly journals Immunopeptidomics for Dummies: Detailed Experimental Protocols and Rapid, User-Friendly Visualization of MHC I and II Ligand Datasets with MhcVizPipe

2020 ◽  
Author(s):  
Kevin A. Kovalchik ◽  
Laura Wessling ◽  
Frederic Saab ◽  
Qing Ma ◽  
Jérôme Despault ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Software Tool ◽  
Class I ◽  
Mhc I ◽  
Binding Motifs ◽  
Histocompatibility Complex ◽  
Starting Point ◽  
Technical Report ◽  
Experimental Protocols ◽  
User Friendly

ABSTRACTImmunopeptidomics refers to the science of investigating the composition and dynamics of peptides presented by major histocompatibility complex (MHC) class I and class II molecules using mass spectrometry (MS). Here, we aim to provide a technical report to any non-expert in the field wishing to establish and/or optimize an immunopeptidomic workflow with relatively limited computational knowledge and resources. To this end, we thoroughly describe step-by-step instructions to isolate MHC class I and II-associated peptides from various biological sources, including mouse and human biospecimens. Most notably, we created MhcVizPipe (MVP) (https://github.com/CaronLab/MhcVizPipe), a new and easy-to-use open-source software tool to rapidly assess the quality and the specific enrichment of immunopeptidomic datasets upon the establishment of new workflows. In fact, MVP enables intuitive visualization of multiple immunopeptidomic datasets upon testing sample preparation protocols and new antibodies for the isolation of MHC class I and II peptides. In addition, MVP enables the identification of unexpected binding motifs and facilitates the analysis of non-canonical MHC peptides. We anticipate that the experimental and bioinformatic resources provided herein will represent a great starting point for any non-expert and will therefore foster the accessibility and expansion of the field to ultimately boost its maturity and impact.

scholarly journals The Secret Lives of Fluorescent Membrane Probes as Revealed by Molecular Dynamics Simulations

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3424
Author(s):  
Hugo A. L. Filipe ◽  
Maria João Moreno ◽  
Luís M. S. Loura
Keyword(s):  
Molecular Dynamics ◽  
Membrane System ◽  
Md Simulations ◽  
Fluorescence Probes ◽  
Host Membrane ◽  
Tremendous Progress ◽  
Long Time ◽  
Experimental Approaches ◽  
Dynamics Simulations ◽  
Membrane Probes

Fluorescent probes have been employed for more than half a century to study the structure and dynamics of model and biological membranes, using spectroscopic and/or microscopic experimental approaches. While their utilization has led to tremendous progress in our knowledge of membrane biophysics and physiology, in some respects the behavior of bilayer-inserted membrane probes has long remained inscrutable. The location, orientation and interaction of fluorophores with lipid and/or water molecules are often not well known, and they are crucial for understanding what the probe is actually reporting. Moreover, because the probe is an extraneous inclusion, it may perturb the properties of the host membrane system, altering the very properties it is supposed to measure. For these reasons, the need for independent methodologies to assess the behavior of bilayer-inserted fluorescence probes has been recognized for a long time. Because of recent improvements in computational tools, molecular dynamics (MD) simulations have become a popular means of obtaining this important information. The present review addresses MD studies of all major classes of fluorescent membrane probes, focusing in the period between 2011 and 2020, during which such work has undergone a dramatic surge in both the number of studies and the variety of probes and properties accessed.

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