Protein structure prediction servers at University College London

A number of state-of-the-art protein structure prediction servers have been developed by researchers working in the Bioinformatics Unit at University College London. The popular PSIPRED server allows users to perform secondary structure prediction, transmembrane topology prediction and protein fold recognition. More recent servers include DISOPRED for the prediction of protein dynamic disorder and DomPred for domain boundary prediction.

The PSIPRED protein structure prediction server

The PSIPRED protein structure prediction server allows users to submit a protein sequence, perform a prediction of their choice and receive the results of the prediction both textually via e-mail and graphically via the web. The user may select one of three prediction methods to apply to their sequence: PSIPRED, a highly accurate secondary structure prediction method; MEMSAT 2, a new version of a widely used transmembrane topology prediction method; or GenTHREADER, a sequence profile based fold recognition method.

Peptide inhibitors of G protein-coupled receptor kinases

G protein-coupled receptor kinases (GRKs) are regulatory enzymes involved in the modulation of seven-transmembrane-helix receptors. In order to develop specific inhibitors for these kinases, we synthesized and investigated peptide inhibitors derived from the sequence of the first intracellular loop of the beta(2)-adrenergic receptor. Introduction of changes in the sequence and truncation of N- and C-terminal amino acids increased the inhibitory potency by a factor of 40. These inhibitors not only inhibited the prototypical GRK2 but also GRK3 and GRK5. In contrast there was no inhibition of protein kinase C and protein kinase A even at the highest concentration tested. The peptide with the sequence AKFERLQTVTNYFITSE inhibited GRK2 with an IC50 of 0.6 mu M, GRK3 with 2.6 mu M and GRK5 with 1.6 mu M. The peptide inhibitors were non-competitive for receptor and ATP. These findings demonstrate that specific peptides can inhibit GRKs in the submicromolar range and suggest that a further decrease in size is possible without losing the inhibitory potency. (c) 2005 Published by Elsevier Inc.

Benchmarking secondary structure prediction for fold recognition

If secondary structure predictions are to be incorporated into fold recognition methods, an assessment of the effect of specific types of errors in predicted secondary structures on the sensitivity of fold recognition should be carried out. Here, we present a systematic comparison of different secondary structure prediction methods by measuring frequencies of specific types of error. We carry out an evaluation of the effect of specific types of error on secondary structure element alignment (SSEA), a baseline fold recognition method. The results of this evaluation indicate that missing out whole helix or strand elements, or predicting the wrong type of element, is more detrimental than predicting the wrong lengths of elements or overpredicting helix or strand. We also suggest that SSEA scoring is an effective method for assessing accuracy of secondary structure prediction and perhaps may also provide a more appropriate assessment of the “usefulness” and quality of predicted secondary structure, if secondary structure alignments are to be used in fold recognition.

On the impact of humidity observations in numerical weather prediction

The impact of humidity observations on forecast skill is explored by producing a series of global forecasts using initial data derived from the ERA-40 reanalyses system, in which all humidity data have been removed during the data assimilation. The new forecasts have been compared with the original ERA-40 analyses and forecasts made from them. Both sets of forecasts show virtually identical prediction skill in the extratropics and the tropics. Differences between the forecasts are small and undergo characteristic amplification rate. There are larger differences in temperature and geopotential in the tropics but the differences are small-scale and unstructured and have no noticeable effect on the skill of the wind forecasts. The results highlight the current very limited impact of the humidity observations, used to produce the initial state, on the forecasts.

The predictability of extratropical storm tracks and the sensitivity of their prediction to the observing system

A new method for assessing forecast skill and predictability that involves the identification and tracking of extratropical cyclones has been developed and implemented to obtain detailed information about the prediction of cyclones that cannot be obtained from more conventional analysis methodologies. The cyclones were identified and tracked along the forecast trajectories, and statistics were generated to determine the rate at which the position and intensity of the forecasted storms diverge from the analyzed tracks as a function of forecast lead time. The results show a higher level of skill in predicting the position of extratropical cyclones than the intensity. They also show that there is potential to improve the skill in predicting the position by 1 - 1.5 days and the intensity by 2 - 3 days, via improvements to the forecast model. Further analysis shows that forecasted storms move at a slower speed than analyzed storms on average and that there is a larger error in the predicted amplitudes of intense storms than the weaker storms. The results also show that some storms can be predicted up to 3 days before they are identified as an 850-hPa vorticity center in the analyses. In general, the results show a higher level of skill in the Northern Hemisphere (NH) than the Southern Hemisphere (SH); however, the rapid growth of NH winter storms is not very well predicted. The impact that observations of different types have on the prediction of the extratropical cyclones has also been explored, using forecasts integrated from analyses that were constructed from reduced observing systems. A terrestrial, satellite, and surface-based system were investigated and the results showed that the predictive skill of the terrestrial system was superior to the satellite system in the NH. Further analysis showed that the satellite system was not very good at predicting the growth of the storms. In the SH the terrestrial system has significantly less skill than the satellite system, highlighting the dominance of satellite observations in this hemisphere. The surface system has very poor predictive skill in both hemispheres.

The prediction of extratropical storm tracks by the ECMWF and NCEP ensemble prediction systems

The prediction of extratropical cyclones by the European Centre for Medium Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) Ensemble Prediction Systems (EPS) has been investigated using an objective feature tracking methodology to identify and track the cyclones along the forecast trajectories. Overall the results show that the ECMWF EPS has a slightly higher level of skill than the NCEP EPS in the northern hemisphere (NH). However in the southern hemisphere (SH), NCEP has higher predictive skill than ECMWF for the intensity of the cyclones. The results from both EPS indicate a higher level of predictive skill for the position of extratropical cyclones than their intensity and show that there is a larger spread in intensity than position. Further analysis shows that the predicted propagation speed of cyclones is generally too slow for the ECMWF EPS and show a slight bias for the intensity of the cyclones to be overpredicted. This is also true for the NCEP EPS in the SH. For the NCEP EPS in the NH the intensity of the cyclones is underpredicted. There is small bias in both the EPS for the cyclones to be displaced towards the poles. For each ensemble forecast of each cyclone, the predictive skill of the ensemble member that best predicts the cyclones position and intensity was computed. The results are very encouraging showing that the predictive skill of the best ensemble member is significantly higher than that of the control forecast in terms of both the position and intensity of the cyclones. The prediction of cyclones before they are identified as 850 hPa vorticity centers in the analysis cycle was also considered. It is shown that an indication of extratropical cyclones can be given by at least 1 ensemble member 7 days before they are identified in the analysis. Further analysis of the ECMWF EPS shows that the ensemble mean has a higher level of skill than the control forecast, particularly for the intensity of the cyclones, 2 from day 3 of the forecast. There is a higher level of skill in the NH than the SH and the spread in the SH is correspondingly larger. The difference between the ensemble mean and spread is very small for the position of the cyclones, but the spread of the ensemble is smaller than the ensemble mean error for the intensity of the cyclones in both hemispheres. Results also show that the ECMWF control forecast has ½ to 1 day more skill than the perturbed members, for both the position and intensity of the cyclones, throughout the forecast.

Storm tracking and ensemble prediction

The prediction of extratropical cyclones by the European Centre for Medium Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) Ensemble Prediction Systems (EPS) is investigated using a storm-tracking forecast verifica-tion methodology. The cyclones are identified and tracked along the forecast trajectories so that statistics can be generated to determine the rate at which the position and intensity of the forecasted cyclones diverge from the corresponding analysed cyclones with forecast time. Overall the ECMWF EPS has a slightly higher level of performance than the NCEP EPS. However, in the southern hemisphere the NCEP EPS has a slightly higher level of skill for the intensity of the storms. The results from both EPS indicate a higher level of predictive skill for the position of extratropical cyclones than their intensity and show that there is a larger spread in intensity than position. The results also illustrate several benefits an EPS can offer over a deterministic forecast.

Data assimilation for morphodynamic prediction and predictability

This paper gives an overview of the project Changing Coastlines: data assimilation for morphodynamic prediction and predictability. This project is investigating whether data assimilation could be used to improve coastal morphodynamic modeling. The concept of data assimilation is described, and the benefits that data assimilation could bring to coastal morphodynamic modeling are discussed. Application of data assimilation in a simple 1D morphodynamic model is presented. This shows that data assimilation can be used to improve the current state of the model bathymetry, and to tune the model parameter. We now intend to implement these ideas in a 2D morphodynamic model, for two study sites. The logistics of this are considered, including model design and implementation, and data requirement issues. We envisage that this work could provide a means for maintaining up-to-date information on coastal bathymetry, without the need for costly survey campaigns. This would be useful for a range of coastal management issues, including coastal flood forecasting.