3DPatch: fast sequence and structure residue-level information content annotation in a web browser

David Jakubec^1,2,∗, Jiří Vondrášek¹, Robert D. Finn³

¹Department of Bioinformatics, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 166 10 Prague 6, Czech Republic

²Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, 128 43 Prague 2, Czech Republic

³European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK

^∗To whom correspondence should be addressed. Email: ^{david.jakubec@uochb.cas.cz}

Amino acid residues manifesting high levels of conservation are often indicative of functionally

significant regions of protein structures. Residues critical for protein folding, hydrophobic core stabilization, intermolecular recognition, or enzymatic activity often manifest lower mutation rates compared to the rest of the protein. Quantitative assessment of residue conservation typically involves querying a sequence against a database, finding similar sequences, aligning them to bring equivalent positions into register, and applying an information theory-based measure to individual columns in the multiple sequence alignment. Understanding how the sequence conservation profile relates in 3D requires its projection onto a protein structure, which can be a time-consuming process.

We developed 3DPatch, a client-side web application that simplifies the task of calculating protein sequence information content, 3D structure identification, and conservation level-based mark-up (Figure 1). 3DPatch utilizes the power of profile hidden Markov models and speed of HMMER3.1 to provide accurate results in a matter of seconds. It was developed with easy integration into other peoples’ websites in mind and supports most modern web browsers. 3DPatch is freely available at http://www.skylign.org/3DPatch/.

Figure 1: Detail of HIV-1 reverse transcriptase in complex with an inhibitor (PDB code 3lp0) marked-up with residue information content using 3DPatch. Higher conservation is indicated with darker colors. Catalytic/ligand binding pocket residues are clearly distinguished based on conservation level.