Abstract Motivation: Identification of protein–ligand binding sites is critical to protein function annotation and drug discovery. However, there no method that could generate optimal site prediction for different types. Combination complementary predictions probably the most reliable solution problem. Results: We develop two new methods, one based on binding-specific substructure comparison (TM-SITE) another sequence profile alignment (S-SITE), predictions. The methods are tested a set 500...

BioLiP (http://zhanglab.ccmb.med.umich.edu/BioLiP/) is a semi-manually curated database for biologically relevant ligand–protein interactions. Establishing interactions between protein and ligands an important step toward understanding the functions. Most ligand-binding sites prediction methods use structures from Protein Data Bank (PDB) as templates. However, not all present in PDB are relevant, small molecules often used additives solving structures. To facilitate template-based docking,...

We have developed a new COFACTOR webserver for automated structure-based protein function annotation. Starting from structural model, given by either experimental determination or computational modeling, first identifies template proteins of similar folds and functional sites threading the target structure through three representative libraries that known protein–ligand binding interactions, Enzyme Commission number Gene Ontology terms. The biological insights in these aspects are then...

I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative assembly simulations. In CASP9 experiments, two new algorithms, QUARK fragment-guided molecular dynamics (FG-MD), were added to the improving structural modeling accuracy. a de novo algorithm used of proteins that lack detectable template structures. For distantly homologous targets, models are found useful as reference selecting good guiding FG-MD atomic-level...

Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. show that BAPs experiencing epileptic seizures or drug-induced effects have substantially reduced complexity (entropy), similar...

Genome sequencing projects have ciphered millions of protein sequence, which require knowledge their structure and function to improve the understanding biological role. Although experimental methods can provide detailed information for a small fraction these proteins, computational modeling is needed majority molecules are experimentally uncharacterized. The I-TASSER server an on-line workbench high-resolution function. Given typical output from includes secondary prediction, predicted...

Shape-based alignment of small molecules is a widely used approach in computer-aided drug discovery. Most shape-based ligand structure applications, both commercial and freely available ones, use the Tanimoto coefficient or similar functions for evaluating molecular similarity. Major drawbacks using such are size dependence score fact that statistical significance match metrics not reported.We describe new open-source virtual screening (VS) algorithm, LIGSIFT, uses Gaussian shape overlay...

Alternative splicing allows a single gene to generate multiple mRNA transcripts, which can be translated into functionally diverse proteins. However, experimentally determined structures of protein splice isoforms are rare, and homology modeling methods poor at predicting atomic-level structural differences because high sequence identity. Here we exploit the state-of-the-art structure prediction method I-TASSER analyze functional consequences alternative proteins differentially expressed in...

Often in pharmaceutical research the goal is to identify small molecules that can interact with and appropriately modify biological behavior of a new protein target. Unfortunately, most proteins lack both known structures molecule binders, prerequisites many virtual screening, VS, approaches. For such proteins, ligand homology modeling, LHM, copies ligands from homologous perhaps evolutionarily distant template has been shown be powerful VS approach possible binding ligands. However, if we...

Hydrogen constitutes nearly half of all atoms in proteins and their positions are essential for analyzing hydrogen-bonding interactions refining atomic-level structures. However, most protein structures determined by experiments or computer prediction lack hydrogen coordinates. We present a new algorithm, HAAD, to predict the based on heavy atoms. The algorithm is built basic rules orbital hybridization followed optimization steric repulsion electrostatic interactions. tested using three...

Genome sequencing projects have ciphered millions of protein sequence, which require knowledge their structure and function to improve the understanding biological role. Although experimental methods can provide detailed information for a small fraction these proteins, computational modeling is needed majority molecules are experimentally uncharacterized. The I-TASSER server an on-line workbench high-resolution function. Given typical output from includes secondary prediction, predicted...

The number of available protein sequences in public databases is increasing exponentially. However, a significant percentage these lack functional annotation, which essential for the understanding how biological systems operate. Here, we propose novel method, Quantitative Annotation Unknown STructure (QAUST), to infer functions, specifically Gene Ontology (GO) terms and Enzyme Commission (EC) numbers. QAUST uses three sources information: structure information encoded by global local...

Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship protein. contains three domains plus ubiquitin-like and an in-between-RING (IBR) domain. are rich cysteine amino acids that act ligands bind zinc ions. may interact with DNA or other perform wide range functions. Some function E3 ubiquitin ligases, participating attachment chains signal...

Using a large database of protein domain families known 3-D structure we present an analysis on the relationships among sequences, structures and functions closely-related enzymes performed at level catalytic domains. Only in 38%

Abstract Most of the pre‐mRNAs in eukaryotic cell are comprised protein‐coding exons and non‐protein‐coding introns. The introns removed ligated together, or spliced, by a large, macromolecular complex known as spliceosome. This RNA‐protein assembly is made up five uridine‐rich small nuclear RNAs (U1‐, U2‐, U4‐, U5‐ U6‐snRNA) well over 300 proteins, which form ribonucleoprotein particles (snRNPs). Initial recognition 5′ exon/intron splice site mediated U1 snRNP, composed snRNA at least ten...