A5103240136- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Image and Signal Denoising Methods
- AI in cancer detection
- DNA and Nucleic Acid Chemistry
- Spectroscopy and Quantum Chemical Studies
- Glycosylation and Glycoproteins Research
- Advanced Image Processing Techniques
- Advanced Image Fusion Techniques
- Photoacoustic and Ultrasonic Imaging
- Cutaneous Melanoma Detection and Management
- Enzyme Structure and Function
- Radiomics and Machine Learning in Medical Imaging
- Medical Imaging Techniques and Applications
- Advanced Image and Video Retrieval Techniques
- Advanced Vision and Imaging
- Theoretical and Computational Physics
- Viral Infectious Diseases and Gene Expression in Insects
- 14-3-3 protein interactions
- Advanced Malware Detection Techniques
- Medical Image Segmentation Techniques
- Scientific Research and Discoveries
- Microfluidic and Capillary Electrophoresis Applications
- Network Security and Intrusion Detection
Simon Fraser University
2018-2024
Shiraz University of Technology
2024
Hamedan University of Technology
2024
Islamic Azad University of Hamedan
2024
Sunesis (United States)
2024
University of Isfahan
2023
La Roche College
2023
Bridge University
2022
Virginia Tech
2013-2017
Amirkabir University of Technology
2010-2016
AmberTools is a free and open-source collection of programs used to set up, run, analyze molecular simulations. The newer features contained within AmberTools23 are briefly described in this Application note.
Simplified classical water models are currently an indispensable component in practical atomistic simulations. Yet, despite several decades of intense research, these still far from perfect. Presented here is alternative approach to constructing widely used point charge models. In contrast the conventional approach, we do not impose any geometry constraints on model other than symmetry. Instead, optimize distribution charges best describe "electrostatics" molecule. The resulting "optimal"...
Classical 3-point rigid water models are most widely used due to their computational efficiency. Recently, we introduced a new approach constructing classical [S. Izadi et al., J. Phys. Chem. Lett. 5, 3863 (2014)], which permits virtually exhaustive search for globally optimal model parameters in the sub-space that is relevant electrostatic properties of molecule liquid phase. Here apply develop Optimal Point Charge (OPC3) model. OPC3 significantly more accurate than commonly same class...
Modern simulation and modeling approaches to investigation of biomolecular structure function rely heavily on a variety methods—water models—to approximate the influence solvent. We give brief overview several distinct classes available water models, with emphasis conceptual basis at each level approximation. The main focus is models most widely used in atomistic simulations, including popular implicit explicit solvent models. Among latter, nonpolarizable N ‐point are covered detail, some...
Unconstrained atomistic simulations of intrinsically disordered proteins and peptides (IDP) remain a challenge: widely used, "general purpose" water models tend to favor overly compact structures relative experiment. Here we have performed total 93 μs unrestrained MD explore, in the context IDPs, recently developed "general-purpose" 4-point rigid model OPC, which describes liquid state close We demonstrate that together with popular AMBER force field ff99SB, offers noticeable improvement...
Subcutaneous injection is the preferred route of administration for many antibody therapeutics reasons that include its speed and convenience. However, small volume limit (typically ≤2 mL) subcutaneous delivery often necessitates formulations at high concentrations (commonly ≥100 mg/mL), which may lead to physicochemical problems. For example, antibodies with large hydrophobic or charged patches can be prone self-interaction giving rise viscosity. Here, we combined X-ray crystallography...
Tolerance to image variations (e.g., translation, scale, pose, illumination, background) is an important desired property of any object recognition system, be it human or machine. Moving towards increasingly bigger datasets has been trending in computer vision especially with the emergence highly popular deep learning models. While being very useful for invariance inter-and intra-class shape variability, these large-scale wild are not other parameters urging researchers resort tricks...
Fc galactosylation is a critical quality attribute for anti-tumor recombinant immunoglobulin G (IgG)-based monoclonal antibody (mAb) therapeutics with complement-dependent cytotoxicity (CDC) as the mechanism of action. Although correlation between and CDC has been known, underlying structure–function relationship unclear. Heterogeneity N-glycosylation produced by Chinese hamster ovary (CHO) cell culture biomanufacturing process leads to variable potency. Here, we derived kinetic model...
Abstract The RAS–RAF pathway is one of the most commonly dysregulated in human cancers 1–3 . Despite decades study, understanding molecular mechanisms underlying dimerization and activation 4 kinase RAF remains limited. Recent structures inactive monomer 5 active dimer 5–8 bound to 14-3-3 9,10 have revealed by which stabilizes both conformations via specific phosphoserine residues. Prior dimerization, protein phosphatase 1 catalytic subunit (PP1C) must dephosphorylate N-terminal (NTpS) 11...
In silico assessment of antibody developability during early lead candidate selection and optimization is paramount importance, offering a rapid material-free screening approach. However, the predictive power reproducibility such methods depend heavily on molecular descriptors, model parameters, accuracy predicted structure models, conformational sampling techniques. Here, we present set surface descriptors specifically designed for predicting developability. We assess performance these by...
The accuracy of skin lesion segmentation has increased in recent years, thanks to advances machine learning techniques and a large influx dermoscopy images. However, there is still room for improvement as exist many considerable challenges mainly due the variability appearance lesions (i.e., shape, size, texture, occlusions). In this work, we present novel approach through leveraging generative adversarial networks. Our consists two models: fully convolutional neural network designed...
Molecular dynamics (MD) simulations based on the implicit solvent generalized Born (GB) models can provide significant computational advantages over traditional explicit simulations. However, standard GB becomes prohibitively expensive for all-atom of large structures; model scales poorly, ∼n2, with number solute atoms. Here we combine our recently developed optimal point charge approximation (OPCA) hierarchical partitioning (HCP) to present an ∼n log n multiscale, yet fully atomistic,...
Some antibodies exhibit elevated viscosity at high concentrations, making them poorly suited for therapeutic applications requiring administration by injection such as subcutaneous or ocular delivery. Here we studied an anti-IL-13/IL-17 bispecific IgG4 antibody, which has anomalously compared to its parent monospecific antibodies. The of the in solution was decreased only ~30% presence NaCl, suggesting electrostatic interactions are insufficient fully explain drivers viscosity. Intriguingly,...
We investigate the effect of solvent models on computed thermodynamics protein folding. Atomistic folding simulations a fast-folding mini-protein, CLN025, were employed to compare two commonly used explicit water models, TIP3P and TIP4P/Ew, one implicit (AMBER generalized Born) model. Although all three correctly identify same native folded state (RMSD = 1.5 ± 0.1 Å relative experimental structure), corresponding free energy landscapes vary drastically between models: almost an...
Binding of antibodies to their receptors is a core component the innate immune system. Understanding precise interactions between and Fc has led engineering novel mAb biotherapeutics with tailored biological activities. One most significant findings that afucosylated monoclonal demonstrate increased affinity toward receptor FcγRIIIa, commensurate increase in antibody-dependent cellular cytotoxicity. Crystal structure analysis hypothesis afucosylation region results reduced steric hindrance...
Accurate yet efficient computational models of solvent environment are central for most calculations that rely on atomistic modeling, such as prediction protein-ligand binding affinities. In this study, we evaluate the accuracy a recently developed generalized Born implicit model, GBNSR6 (Aguilar et al. J. Chem. Theory Comput. 2010, 6, 3613-3639), in estimating electrostatic solvation free energies (ΔG(pol)) and (ΔΔG(pol)) small complexes. We also compare estimates based three different...
Medical image segmentation annotations suffer from inter- and intra-observer variations even among experts due to intrinsic differences in human annotators ambiguous boundaries. Leveraging a collection of annotators' opinions for an is interesting way estimating gold standard. Although training deep models supervised setting with single annotation per has been extensively studied, generalizing their work datasets containing multiple remains fairly unexplored problem. In this paper, we...
Deamidation of asparagine (Asn) and isomerization aspartic acid (Asp) residues are among the most commonly observed spontaneous post-translational modifications (PTMs) in proteins. Understanding predicting a protein sequence's propensity for such PTMs can help expedite therapeutic discovery development. In this study, we used proton-affinity calculations with semi-empirical quantum mechanics microsecond long equilibrium molecular dynamics simulations to investigate mechanistic roles...
In positron emission tomography (PET), attenuation and scatter corrections are necessary steps toward accurate quantitative reconstruction of the radiopharmaceutical distribution. Inspired by recent advances in deep learning, many algorithms based on convolutional neural networks have been proposed for automatic correction, enabling applications to CT-less or MR-less PET scanners improve performance presence CT-related artifacts. A known characteristic imaging is varying tracer uptakes...
Fast and accurate calculation of solvation free energies is central to many applications, such as rational drug design. In this study, we present a grid-based molecular surface implementation "R6" flavor the generalized Born (GB) implicit solvent model, named GBNSR6. The speed, accuracy relative numerical Poisson-Boltzmann treatment, sensitivity grid parameters are tested on set 15 small protein-ligand complexes biomolecules in range 268 25099 atoms. Our results demonstrate that proposed...