A5008845398- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Parkinson's Disease Mechanisms and Treatments
- Voice and Speech Disorders
- Autism Spectrum Disorder Research
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- Alzheimer's disease research and treatments
- Chemical Synthesis and Analysis
- Neurological disorders and treatments
- Congenital gastrointestinal and neural anomalies
- Free Radicals and Antioxidants
- Advanced biosensing and bioanalysis techniques
- Gene Regulatory Network Analysis
- Protein Interaction Studies and Fluorescence Analysis
- Axon Guidance and Neuronal Signaling
- Microbial Metabolic Engineering and Bioproduction
- Genetic Associations and Epidemiology
- Drug Transport and Resistance Mechanisms
Biogen (United States)
2016-2024
Pfizer (United States)
2024
Massachusetts General Hospital
2022-2023
Harvard University
2023
Massachusetts Institute of Technology
2023
Mass General Brigham
2023
MGH Institute of Health Professions
2023
Athinoula A. Martinos Center for Biomedical Imaging
2023
Johns Hopkins University
2010-2017
University of Baltimore
2013
Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease. Biochemical and structural analyses show that aducanumab binds linear epitope formed by amino acids 3-7 Aβ peptide. Aducanumab discriminates between monomers oligomeric or fibrillar aggregates based on weak monovalent affinity, fast binding kinetics strong avidity epitope-rich aggregates. Direct comparative studies with analogs gantenerumab, bapineuzumab...
Abstract Digital health technologies can provide continuous monitoring and objective, real-world measures of Parkinson’s disease (PD), but have primarily been evaluated in small, single-site studies. In this 12-month, multicenter observational study, we whether a smartwatch smartphone application could measure features early PD. 82 individuals with early, untreated PD 50 age-matched controls wore research-grade sensors, smartwatch, while performing standardized assessments the clinic. At...
Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state predictive methodology. Here we describe a community-wide assessment methods to predict effects mutations on protein-protein interactions. Twenty-two groups predicted comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful...
Peptidomimetics are classes of molecules that mimic structural and functional attributes polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic finding broad applications for molecular recognition inhibiting protein-protein interactions. One critical limitation is the limited set design tools identifying oligomer sequences adopt desired conformations. Here, we...
Abstract In CAPRI rounds 13–19, the most native‐like structure predicted by RosettaDock resulted in two high, one medium, and acceptable accuracy model out of 13 targets. The current were especially challenging with many unbound homology modeled starting structures. Novel docking methods, including EnsembleDock SnugDock, allowed backbone conformational sampling during enabled creation more accurate models. For Target 32, α‐amylase/subtilisin inhibitor‐subtilisin savinase, we sampled...
We report the first assessment of blind predictions water positions at protein-protein interfaces, performed as part critical predicted interactions (CAPRI) community-wide experiment. Groups submitting docking for complex DNase domain colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict interfacial molecules using method their choice. The predictions-20 groups submitted a total 195 models-were assessed by measuring recall fraction water-mediated contacts. Of 176...
Antibody-antigen interactions are critical to our immune response, and understanding the structure-based biophysical determinants for their binding specificity affinity is of fundamental importance. We present a computational cross-docking study test identification native antibody-antigen interaction pairs among cognate non-cognate complexes. picked dataset 17 complexes which 11 have both bound unbound structures available, we generated representative ensemble Using Rosetta interface score...
Little is known about the effects of single DNA methylation events on gene transcription. The ability to direct toward a unique site within genome would have broad use as tool study specific epigenetic changes A targeted enzyme might also be useful in therapy for diseases with an component or means site-specifically label DNA. Previous studies sought target methyltransferase activity by fusing binding proteins methyltransferases. However, domain remains active even when protein unbound,...
Abstract Smartphones and wearables are widely recognised as the foundation for novel Digital Health Technologies (DHTs) clinical assessment of Parkinson’s disease. Yet, only limited progress has been made towards their regulatory acceptability effective drug development tools. A key barrier in achieving this goal relates to influence a wide range sources variability (SoVs) introduced by measurement processes incorporating DHTs, on ability detect relevant changes PD. This paper introduces...
ABSTRACT Rounds 20–27 of the Critical Assessment PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address wide range challenges. The diverse targets drove creation and new combinations tools. In this study, RosettaDock other novel Rosetta protocols were used successfully predict four 10 blind targets. For example, DNase domain Colicin E2–Im2 immunity protein, RosettaLigand positions water molecules at interface, recovering 46% native...
Protein-protein interactions depend on a host of environmental factors. Local pH conditions influence the through protonation states ionizable residues that can change upon binding. In this work, we present pH-sensitive docking approach, pHDock, sample side-chain five (Asp, Glu, His, Tyr, Lys) on-the-fly during simulation. pHDock produces successful local funnels in approximately half (79/161) protein complexes, including 19 cases where standard RosettaDock fails. also performs better than...
Abstract Digital health technologies can provide continuous monitoring and objective, real world measures of Parkinson’s disease (PD), but have primarily been evaluated in small, single-site studies. In this 12-month, multicenter observational study, we whether a smartwatch smartphone application could measure features early PD. 82 individuals with early, untreated PD 50 age-matched controls wore research-grade sensors, smartwatch, while performing standardized assessments clinic. At home,...
Abstract A high-quality map of the human protein–protein interaction (PPI) network can help us better understand complex genotype–phenotype relationships. Each edge between two interacting proteins supported through an interface in a three-dimensional (3D) structure protein adds credibility to biological relevance interaction. Such structure-supported interactions would augment primarily built using high-throughput cell-based biophysical methods. Here, we integrate structural information...
There is an error in Figures 1-4, Figure S1 and Model S1. The authors made their model which resulted a shift where the HS1 HS2 zinc fingers are predicted to bind. Please view correct here: Figure 1: Figure 2: 3: 4: S1: Click here for additional data file.(2.2M, tif) Model file.(5.8M, zip)
There has been a renewed interest in immunotherapy targeting Aβ peptide for treatment of Alzheimer’s disease (AD) with the intriguing Phase 1b findings showing aducanumab significantly reduces amyloid patients’ brains. Hypotheses being investigated positive clinical data are preferred epitope and selectivity toxic aggregates. Aducanumab (BIIB037) is human monoclonal antibody derived from healthy donor cohort elderly subjects lacking signs cognitive impairment, which advanced testing AD....
We describe a next-generation Drosophila Protein Interaction Map – “DPIM2” established from affinity purification-mass spectrometry of 5,805 baits covering the largest fraction yet proteome. The final network contains 32,668 interactions among 3,644 proteins, organized into 632 clusters representing putative functional modules. Our analysis significantly expands pool known protein in , provides wealth annotation for poorly studied genes and, importantly, postulates previously undescribed...