A5060147489- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Machine Learning in Bioinformatics
- Microbial Metabolic Engineering and Bioproduction
- Protein Degradation and Inhibitors
- Chemical Synthesis and Analysis
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Bioinformatics and Genomic Networks
- Bacterial Genetics and Biotechnology
- Machine Learning in Materials Science
- Transgenic Plants and Applications
- Microbial Natural Products and Biosynthesis
- DNA and Nucleic Acid Chemistry
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Estrogen and related hormone effects
- Mass Spectrometry Techniques and Applications
Stony Brook University
2016-2025
Boston University
2010-2023
State University of New York
2023
European Bioinformatics Institute
2020
Statistics Finland
2016
Hebrew University of Jerusalem
2012-2015
New York Structural Biology Center
2014
Wentworth Institute of Technology
2011-2013
Acpharis
2013
North Carolina State University
2009
Abstract The Fast Fourier Transform (FFT) correlation approach to protein–protein docking can evaluate the energies of billions docked conformations on a grid if energy is described in form function. Here, this restriction removed, and efficiently used with pairwise interaction potentials that substantially improve results. basic idea approximating matrix by its eigenvectors corresponding few dominant eigenvalues, resulting an expression written as sum functions, solving problem repeated FFT...
ABSTRACT The protein docking server ClusPro has been participating in critical assessment of prediction interactions (CAPRI) since its introduction 2004. This article evaluates the performance 2.0 for targets 46–58 Rounds 22–27 CAPRI. analysis leads to a number important observations. First, reliably yields acceptable or medium accuracy models moderate difficulty that have also successfully predicted by other groups, and fails only few submitted. Second, quality automated is very close best...
The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) removal steric clashes by minimization. In response to challenges encountered in recent CAPRI targets, we added new options ClusPro. These are accounting for small angle X-ray scattering data docking; considering pairwise interaction restraints; enabling discrimination between biological...
The binding sites of proteins generally contain smaller regions that provide major contributions to the free energy and hence are prime targets in drug design. Screening libraries fragment-sized compounds by NMR or X-ray crystallography demonstrates such 'hot spot' bind a large variety small organic molecules, relatively high 'hit rate' is predictive target likely drug-like ligands with affinity. Our goal determine spots' computationally rather than experimentally.We have developed FTMAP...
Binding site identification is a classical problem that important for range of applications, including the structure-based prediction function, elucidation functional relationships among proteins, protein engineering and drug design. We describe an accurate method binding identification, namely FTSite. This based on experimental evidence ligand sites also bind small organic molecules various shapes polarity. The FTSite algorithm does not rely any evolutionary or statistical information, but...
Despite the growing number of examples small-molecule inhibitors that disrupt protein–protein interactions (PPIs), origin druggability such targets is poorly understood. To identify druggable sites in interfaces we combine computational solvent mapping, which explores protein surface using a variety small “probe” molecules, with conformer generator to account for side-chain flexibility. Applications unliganded structures 15 PPI target proteins show comprise cluster binding hot spots,...
Background: The use of alternative flame retardants has increased since the phase out pentabromodiphenyl ethers (pentaBDEs). One alternative, Firemaster® 550 (FM550), induces obesity in rats. Triphenyl phosphate (TPP), a component FM550, structure similar to that organotins, which are obesogenic rodents.Objectives: We tested hypothesis components FM550 biologically active peroxisome proliferator-activated receptor γ (PPARγ) ligands and estimated indoor exposure TPP.Methods: its were assessed...
Abstract We present the results for CAPRI Round 54, 5th joint CASP‐CAPRI protein assembly prediction challenge. The offered 37 targets, including 14 homodimers, 3 homo‐trimers, 13 heterodimers antibody–antigen complexes, and 7 large assemblies. On average ~70 CASP predictor groups, more than 20 automatics servers, submitted models each target. A total of 21 941 by these groups 15 scorer were evaluated using model quality measures DockQ score consolidating measures. performance was quantified...
Abstract Our approach to protein—protein docking includes three main steps. First, we run PIPER, a rigid body program based on the Fast Fourier Transform (FFT) correlation approach, extended use pairwise interactions potentials. Second, 1000 best energy conformations are clustered, and 30 largest clusters retained for refinement. Third, stability of is analyzed by short Monte Carlo simulations, structures refined medium‐range optimization method SDU. The first two steps this implemented in...
Predicting how proteins interact at the molecular level is a computationally intensive task. Many protein docking algorithms begin by using fast Fourier transform (FFT) correlation techniques to find putative rigid body orientations. Most such approaches use 3D Cartesian grids and are therefore limited computing three dimensional (3D) translational correlations. However, FFTs can speed up calculation in only of six degrees freedom, they cannot easily incorporate prior knowledge about complex...
Abstract Motivation: An effective docking algorithm for antibody–protein antigen complex prediction is an important first step toward design of biologics and vaccines. We have recently developed a new class knowledge-based interaction potentials called Decoys as the Reference State (DARS) incorporated DARS into program PIPER based on fast Fourier transform correlation approach. Although was best performer in latest rounds CAPRI protein experiment, it much less accurate pairs than other types...
Deregulation of cap-dependent translation is associated with cancer initiation and progression. The rate-limiting step protein synthesis the loading ribosomes onto mRNA templates stimulated by heterotrimeric complex, eukaryotic factor (eIF)4F. This represents an attractive target for anticancer drug discovery because it resides at nexus TOR signaling pathway. We have undertaken ultra-high-throughput screen to identify inhibitors that prevent assembly eIF4F complex. One identified compounds...
We present the results for CAPRI Round 30, first joint CASP-CAPRI experiment, which brought together experts from protein structure prediction and protein-protein docking communities. The comprised 25 targets amongst those submitted CASP11 experiment of 2014. included mostly homodimers, a few homotetramers, two heterodimers, chains that could readily be modeled using templates Protein Data Bank. On average 24 groups 7 CASP predictions each target, 12 per target participated in scoring...
Binding hot spots, protein sites with high-binding affinity, can be identified using X-ray crystallography or NMR by screening libraries of small organic molecules that tend to cluster at such regions. FTMAP, a direct computational analog the experimental approaches, globally samples surface target as probes, finds favorable positions, clusters conformations and ranks on basis average energy. The regions bind several probe predict binding in good agreement results. Small discovered...
Peptide-protein interactions contribute a significant fraction of the protein-protein interactome. Accurate modeling these is challenging due to vast conformational space associated with highly flexible peptides large receptor surfaces. To address this challenge we developed fragment based high-resolution peptide-protein docking protocol. By streamlining Rosetta picker for accurate peptide ensemble generation, PIPER algorithm exhaustive fragment-receptor rigid-body and FlexPepDock full-atom...
Abstract Summary We present an approach for the efficient docking of peptide motifs to their free receptor structures. Using a motif based search, we can retrieve structural fragments from Protein Data Bank (PDB) that are very similar peptide’s final, bound conformation. use Fast Fourier Transform (FFT) method quickly perform global rigid body these receptor. According CAPRI criteria, acceptable conformation often be found among top-ranking predictions. Availability and Implementation The is...