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O H Crawford

Publications and source records attributed to O H Crawford.

5 recordsLinked to original sources
PubMed2000

A computational method for NMR-constrained protein threading.

Protein threading provides an effective method for fold recognition and backbone structure prediction. But its application is currently limited due to its level of prediction accuracy and scope of applicability. One way to significantly improve its usefulness is through the incorporation of underconstrained (or partial) NMR data. It is well known that the NMR method for protein structure determination applies only to small proteins and that its effectiveness decreases rapidly as the protein mass increases beyond about 30 kD. We present, in this paper, a computational framework for applying underconstrained NMR data (that alone are insufficient for structure determination) as constraints in protein threading and also in all-atom model construction. In this study, we consider both secondary structure assignments from chemical shifts and NOE distance restraints. Our results have shown that both secondary structure assignments and a small number of long-range NOEs can significantly improve the threading quality in both fold recognition and threading-alignment accuracy, and can possibly extend threading's scope of applicability from homologs to analogs. An accurate backbone structure generated by NMR-constrained threading can then provide a great amount of structural information, equivalent to that provided by many NMR data; and hence can help reduce the number of NMR data typically required for an accurate structure determination. This new technique can potentially accelerate current NMR structure determination processes and possibly expand NMR's capability to larger proteins.

Algorithms↗
PubMed1999

A fast, stochastic threading algorithm for proteins.

MOTIVATION: Sequences for new proteins are being determined at a rapid rate, as a result of the Human Genome Project, and related genome research. The ability to predict the three-dimensional structure of proteins from sequence alone would be useful in discovering and understanding their function. Threading, or fold recognition, aims to predict the tertiary structure of a protein by aligning its amino acid sequence with a large number of structures, and finding the best fit. This approach depends on obtaining good performance from both the scoring function, which simulates the free energy for given trial alignments, and the threading algorithm, which searches for the lowest-score alignment. It appears that current scoring functions and threading algorithms need improvement. RESULTS: This paper presents a new threading algorithm. Numerical tests demonstrate that it is more powerful than two popular approximate algorithms, and much faster than exact methods.

Algorithms↗
PubMed1999

Protein threading by PROSPECT: a prediction experiment in CASP3.

We present an analysis of the protein fold recognition experiment using PROSPECT in The Third Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP3). PROSPECT is a computer program we have recently developed for finding an optimal alignment between a protein sequence and a protein structural fold. Two unique features of PROSPECT are (a) that it guarantees to find the globally optimal sequence-structure alignment and does so in an efficient manner, when the alignment-scoring function consists of three additive terms: (i) a singleton fitness term, (ii) a pairwise contact preference term between residues that are spatially close (</=15 A between their beta-carbons) and (iii) an alignment gap penalty; and (b) that it guarantees to find the globally-optimal alignment under various constraints on the unknown protein specified by the user. In the CASP3 experiment, PROSPECT correctly identified the most similar folds for 11 targets and predicted closely-similar folds for five other targets among the 23 targets which can be classified into the category of fold-recognition problems and also had their experimentally-determined structures available. Among the 11 correctly identified folds, PROSPECT obtained good sequence-structure alignments for nine of them. On three of the five ab initio prediction problems, PROSPECT successfully located partial structures from our template library, which align accurately with the corresponding targets.

Amino Acid Sequence↗
PubMed1998

Product yields from irradiated glycylglycine in oxygen-free solutions: Monte Carlo simulations and comparison with experiments.

The radiation chemistry of photon-irradiated aqueous solutions of biological molecules may be considered under four distinct time regimes: physical transport (< or = 10(-15) s); prechemical conversion of H2O+, H2O*, and subexcitation electrons into free radicals and molecular products (10(-15) s to 10(-12) s); chemical reactions within individual electron tracks (10(-12) s to 10(-6) s); and chemical reactions within overlapping tracks (>10(-6) s). We have previously reported of the use of the Monte Carlo radiation transport/chemistry codes OREC and RADLYS to model the radiolysis of glycylglycine in oxygen-free solution to a time of 1 micros. These simulations successfully predicted the yields of free ammonia, an end product created solely in the reaction of the hydrated electron with the solute within individual tracks. Other measurable products are only partially created during intratrack reactions, and thus one must additionally consider the late, intertrack chemistry of this system. In this paper, we extend our simulations of glycylglycine radiolysis to model for the first time the events which occur during this late chemistry stage. The model considers the product rates of the reactants in bulk solution by using previously available microsecond intratrack yields given by single-track OREC/RADLYS simulations and an x-ray dose rate of 2.80 Gy min(-1) as used in a companion experimental program. These rates are then applied in a series of coupled, differential rate equations that describe the solution chemistry of glycylglycine radiolysis. Product yields are reported as a function of time over a total irradiation period of 10(4) s. Excellent overall agreement is seen between the theoretical predictions and measurements of five radiolysis end products: free ammonia, acetylglycine, diaminosuccinic acid, aspartic acid, and succinic acid. The model also gives the explicit contributions of intratrack and intertrack reactions to the various end products. For example, the model predicts that approximately 56% and 93% of succinic acid and aspartic acid, respectively, are produced during intertrack reactions at a solute concentration of 0.05 M; these contributions drop to 0.07% and 11%, respectively, at 1.2 M.

Computer Simulation↗