A5028120169- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Computational Drug Discovery Methods
- Hormonal and reproductive studies
- Viral Infectious Diseases and Gene Expression in Insects
- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Microfluidic and Bio-sensing Technologies
- Machine Learning in Bioinformatics
- Hypothalamic control of reproductive hormones
- Advanced Biosensing Techniques and Applications
- Pharmacological Effects and Assays
- HER2/EGFR in Cancer Research
- Bioinformatics and Genomic Networks
- Chemistry and Chemical Engineering
- Biosimilars and Bioanalytical Methods
- Effects and risks of endocrine disrupting chemicals
University of British Columbia
2008
Family Research Institute
2008
Vancouver General Hospital
2008
Child and Family Research Institute
2008
A blinded study to assess the state of art in three-dimensional structure modeling variable region (Fv) antibodies was conducted. Nine unpublished high-resolution x-ray Fab crystal structures covering a wide range antigen-binding site conformations were used as benchmark compare Fv models generated by four prediction methodologies. The methodologies included two homology strategies independently developed CCG (Chemical Computer Group) and Accerlys Inc, fully automated antibody servers: PIGS...
The early phase of protein drug development has traditionally focused on target binding properties leading to a desired mode therapeutic action. As more therapeutics pass through the pipeline; however, it is clear that non-optimal biophysical can emerge, particularly as proteins are formulated at high concentrations, causing aggregation or polyreactivity. Such late-stage "developability" problems lead delay failure in traversing process. Aggregation propensity also correlated with increased...
Understanding the pharmacokinetic (PK) properties of a drug, such as clearance, is crucial step for evaluating efficacy. The PK therapeutic antibodies can be complex and influenced by interactions with target, Fc-receptors, anti-drug antibodies, antibody intrinsic factors. A growing body literature has linked biophysical particularly nonspecific-binding propensity, hydrophobicity charged regions to rapid clearance in preclinical species selected human studies. clear understanding connection...
The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity pharmacokinetic (PK) clearance predictions. In this work, structure-based descriptors are evaluated their predictive performance recently published pI, viscosity, data. From this, we devised four rules therapeutic profiling which address developability issues arising from charged-based solution behavior, PK, the ability to...
Nonspecific interactions are a key challenge in the successful development of therapeutic antibodies. The tendency for nonspecific binding antibodies is often difficult to reduce by rational design, and instead, it necessary rely on comprehensive screening campaigns. To address this issue, we performed systematic analysis impact surface patch properties antibody nonspecificity using designer library as model system single-stranded DNA ligand. Using an in-solution microfluidic approach, find...
Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack solubility. In this work, we optimized a candidate integrin α11-binding mAb developability using molecular modeling, rational design, hydrophobic interaction chromatography (HIC). A homology model parental Fv region was built, revealed patches on surface...
A benchmark data set of steroids with known affinity for sex hormone-binding globulin (SHBG) has been widely used to validate popular molecular field-based QSAR techniques. We have expanded the by adding a number nonsteroidal SHBG ligands identified both from literature and in our previous experimental studies. This updated herein develop 4D models based on "inductive" descriptors gain insight into basis protein–ligand interactions. Molecular alignment was generated means docking active...
Accurately predicting how a small molecule binds to its target protein is an essential requirement for structure-based drug design (SBDD) efforts. In structurally enabled medicinal chemistry programs, binding pose prediction often applied ligands after related compound's crystal structure bound the has been solved. this article, we present automated protocol that makes extensive use of existing X-ray ligand information. It uses spatial restraints during docking based on maximum common...
Here, we introduce an aligned database of protein kinase structures that can be efficiently explored by sequence, structure, or ATP pocket ligand (type similarity).We also discuss automated protocol for identification, classification and superposition relies on a curated reference set sequences covering the wide variety human kinases.