Advances in structural genomics and protein structure prediction require the design of automatic, fast, objective, well benchmarked methods capable comparing assessing similarity low-resolution three-dimensional structures, via experimental or theoretical approaches. Here, a new method for sequence-independent alignment is presented that allows comparison an with arbitrary tertiary model. The heuristic algorithm given then used to show it can describe random alignments proteins different...

Abstract Exploiting sequence–structure–function relationships in biotechnology requires improved methods for aligning proteins that have low sequence similarity to previously annotated proteins. We develop two deep learning address this gap, TM-Vec and DeepBLAST. allows searching structure–structure similarities large databases. It is trained accurately predict TM-scores as a metric of structural directly from pairs without the need intermediate computation or solution structures. Once...

Abstract A major limitation of current comparative modeling methods is the accuracy with which regions that are structurally divergent from homologues known structure can be modeled. Because structural differences between homologous proteins responsible for variations in protein function and specificity, ability to model these has important functional consequences. Although existing provide reasonably accurate models short loop regions, longer an unsolved problem. Here we describe a method...

Rosetta ab initio protein structure predictions in CASP4 were considerably more consistent and accurate than previous predictions. Large segments correctly predicted (>50 residues superimposed within an RMSD of 6.5 Å) for 16 the 21 domains under 300 which models submitted. Models with global fold largely correct produced several targets new folds, difficult recognition targets, those traditional models. These promising results suggest that may soon be able to contribute interpretation genome...

The Rosetta de novo structure prediction and loop modeling protocols begin with coarse grained Monte Carlo searches in which the moves are based on short fragments extracted from a database of known structures. Here we describe new object oriented program for picking that greatly extends functionality previous (nnmake) opens door approaches to modeling. We provide detailed description code design architecture, highlighting its modularity, features such as extensibility, total control over...

Naturally occurring homooligomeric protein complexes exhibit striking internal symmetry. The evolutionary origins of this symmetry have been the subject considerable speculation; proposals for advantages associated with include greater folding efficiency, reduced aggregation, amenability to allosteric regulation, and adaptability. An alternative possibility stems from idea that contribute fitness, hence be optimization, a complex must significantly populated, which implies interaction energy...

Abstract Many applications require a method for translating large list of bond angles and lengths to precise atomic Cartesian coordinates. This simple but computationally consuming task occurs ubiquitously in modeling proteins, DNA, other polymers as well many fields such robotics. To find an optimal method, algorithms can be compared by number operations, speed, intrinsic numerical stability, parallelization. We discuss five established methods growing protein backbone serial chain...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCorrelations without coincidence measurements: deciding between stepwise and concerted dissociation mechanisms for ABC .-+. A + B CC. E. M. Strauss Paul L. HoustonCite this: J. Phys. Chem. 1990, 94, 25, 8751–8762Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://pubs.acs.org/doi/10.1021/j100388a003https://doi.org/10.1021/j100388a003research-articleACS PublicationsRequest...

We created a single cell sorting system to screen for enzyme activity in Escherichia coli producing 3,4 dihydroxy benzoate (34DHB). To do so, we engineered transcription factor regulon controlling the expression of green fluorescent protein (GFP) induction by 34DHB. An autoregulated factor, pcaU, was borrowed from Acinetobacter sp ADP1 E. and its promoter region adapted Coli. The pcaU inducible at >5 μM exogenous 34DHB, making it sensitive biosensor this industrially significant nylon...

ABSTRACT Structure‐based rational mutagenesis for engineering protein functionality has been limited by the scarcity and difficulty of obtaining crystal structures desired proteins. On other hand, when high‐throughput selection is possible, directed evolution‐based approaches gaining functionalities have random fortuitous with rationalization. We combine comparative modeling dimer structures, ab initio loop reconstruction, ligand docking to select positions create a library focused on...

This study explores the use of multiple sequence alignment (MSA) information and global measures hydrophobic core formation for improving Rosetta ab initio protein structure prediction method. The most effective MSA is achieved by carrying out independent folding simulations a subset homologous sequences in then identifying free energy minima common to all folded via simultaneous clustering runs. Global formation, using ellipsoidal rather than spherical representations core, are found be...

Saccharomyces cerevisiae is one of the best-studied model organisms, yet three-dimensional structure and molecular function many yeast proteins remain unknown. Yeast were parsed into 14,934 domains, those lacking sequence similarity to known folded using Rosetta de novo prediction method on World Community Grid. This structural data was integrated with process, component, annotations from Genome Database assign protein domains SCOP superfamilies a simple Bayesian approach. We have predicted...

A whole-cell biosensor utilizing a transcription factor (TF) is an effective tool for sensitive and selective detection of specialty chemicals or anthropogenic molecules, but requires access to expanded repertoire TFs. Using homology modeling ligand docking binding pocket identification, assisted by conservative mutations in the pocket, we engineered novel specificity Acinetobacter TF, PobR, 'sense' chemical p-nitrophenol (pNP) measured response via fluorescent protein reporter expressed...

Robust fluorescence-based biosensors are emerging as critical tools for high-throughput strain improvement in synthetic biology. Many developed model organisms where sophisticated biology also well established. However, industrial biochemical production often employs microbes with phenotypes that advantageous a target process, and may fail to directly transition outside the host which they developed. In particular, losses sensitivity dynamic range of sensing occur, limiting application...

Product inhibition is a frequent bottleneck in industrial enzymes, and testing mutations to alleviate product via traditional methods remains challenging as many variants need be tested against multiple substrate concentrations. Further, screening are conducted vitro, resulting enzyme may perform differently vivo the context of whole-cell metabolism regulation. In this study, we address these two problems by establishing high-throughput method an industrially relevant enzyme, chorismate...

The photodissociation of OCS at 157 nm has been investigated by using tunable vacuum ultraviolet radiation to probe the CO and S photoproducts. Sulfur is produced almost entirely in 1S state, while its ground electronic state vibrational levels from v=0–3 approximate ratio (v=0):(v=1):(v=2):(v=3)=(1.0):(1.0):(0.5) :(0.3). rotational distribution for each level found be near Boltzmann, with temperatures that decrease 1350 K v=0 780 v=3. Measurements Doppler profiles demonstrate dissociation...

We report the measurement of two-photon detachment spectrum $^{1}D^{e}$ resonance ${\mathrm{H}}^{\ensuremath{-}}$ just below $n\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2$ threshold. The excess photon fits a Fano profile with energy 10.872(2) eV (relative to ground state), width 0.0105(10) eV, and shape parameter $\ensuremath{-}8(2)$. To our knowledge, this describes first time direct multiphoton excitation has been observed in any negative atomic ion.

Recent work has shown how information theory extends conventional full-rationality game to allow bounded rational agents. The associated mathematical framework can be used solve distributed optimization and control problems. This is done by translating the problem into an iterated game, where each agent's mixed strategy (i.e. its stochastically determined move) sets a different variable of problem. So expected value objective function joint probability distribution across moves strategies...

We compare Genetic Algorithms (GA's) with Probability Collectives (PC), a new framework for distributed optimization and control. In contrast to GA's, PC-based methods do not update populations of solutions. Instead they an explicitly parameterized probability distribution p over the space That updating arises as functional p. The is chosen so that any optimizes it should be peaked about good PC approach has deep connections both game theory statistical physics. review using its motivation...

Protein G is an IgG binding protein that has been widely exploited for biotechnological purposes. Rosetta modeling identified a set of favorable polar mutations in G, at its interface with the Fc domain Immunoglobulin were predicted to increase stability and tighten relative native only minor perturbation mode seen crystal structure. This triple mutant was synthesized evaluated experimentally. Relative showed 3.5-fold enhancement display level on surface yeast 5-fold tighter molar affinity...

Abstract Exploiting sequence-structure-function relationships in molecular biology and computational modeling relies on detecting proteins with high sequence similarities. However, the most commonly used alignment-based methods, such as BLAST, frequently fail low similarity to previously annotated proteins. We developed a deep learning method, TM-Vec, that uses alignments learn structural features can then be search for structure-structure similarities large databases. train TM-Vec...