Eckart Bindewald

The SSEA server for protein secondary structure alignment

SUMMARY We present a web server that computes alignments of protein secondary structures. The server supports both performing pairwise alignments and searching a secondary structure against a library of domain folds. It can calculate global and local secondary structure element alignments. A combination of local and global alignment steps can be used to search for domains inside the query sequence or help in the discrimination of novel folds. Both the SCOP and PDB fold libraries, clustered at 95 and 40% sequence identity, are available for alignment. AVAILABILITY The web server interface is freely accessible to academic users at http://protein.cribi.unipd.it/ssea/. The executable version and benchmarking data are available from the same web page.

A scoring function for docking ligands to low-resolution protein structures

We present a docking method that uses a scoring function for protein–ligand docking that is designed to maximize the docking success rate for low‐resolution protein structures. We find that the resulting scoring function parameters are very different depending on whether they were optimized for high‐ or low‐resolution protein structures. We show that this docking method can be successfully applied to predict the ligand‐binding site of low‐resolution structures. For a set of 25 protein–ligand complexes, in 76% of the cases, more than 50% of ligand‐contacting residues are correctly predicted (using receptor crystal structures where the binding site is unspecified). Using decoys of the receptor structures having a 4 Å RMSD from the native structure, for the same set of complexes, in 72% of the cases, we obtain at least one correctly predicted ligand‐contacting residue. Furthermore, using an 81‐protein–ligand set described by Jain, in 76 (93.8%) cases, the algorithm correctly predicts more than 50% of the ligand‐contacting residues when native protein structures are used. Using 3 Å RMSD from native decoys, in all but two cases (97.5%), the algorithm predicts at least one ligand‐binding residue correctly. Finally, compared to the previously published Dolores method, for 298 protein–ligand pairs, the number of cases in which at least half of the specific contacts are correctly predicted is more than four times greater.

Implementing Genetic Algorithms with Sterical Constraints for Protein Structure Prediction

In this paper we present new kinds of genetic operators for protein structure prediction. These operators solve the problem of atom collisions during the conformational search. They restrict the search space to collision-free conformations by enforcing sterical constraints on the protein at each optimization step.

Align: a C++ class library and web server for rapid sequence alignment prototyping.

Sequence alignment remains a fundamental tool in most tasks related to the prediction of protein sequence and structure. A C++ class library was developed to facilitate the rapid implementation of a variety of state-of-the-art pairwise sequence alignment techniques. These range from simple sequence to sequence to the advanced profile to profile alignments with optional secondary structure information. Suboptimal alignments, frequently used to estimate regions of confidence, can also be generated. The object oriented design facilitates rapid implementation, testing and extension of existing functionality. A simple web interface, which can also be useful in bioinformatics education, is also provided. Source code, online documentation and a prototypical web interface are freely accessible to academic users from the URL: http://protein.cribi.unipd.it/align/. A sample case study in the modelling of human Cytochrome P450 is discussed.