Interesting and Useful Tools
Most tools are available as a web interface or a Google Co-Lab/Jupyter notebook. Applications may also be installed on the HPC.
ColabFold
Colabfold uses google colab notebooks to run different versions of Alphafold2 for structure prediction of monomers and protein complexes. The multiple sequence alignment (MSA) step is performed by using mmseqs API (see below) and can be used to generate MSAs for other puproses. There are many different versions of AF2 are available. Due to limitations in available hardware in free tier google colab notebooks it may not be feasible to fold proteins or complexes >2000 aa total.
VEP
VEP is Ensembl’s variant effect predictor. It integrates most common variant annotation tools and databases in a single location. It is available as a command line tool and a web interface for a smaller subset of variants. The command line tool is installed (with numerous annotation packages) in HPC and is available for all users. Many variant effect prediction tools like AlphaMissense, spliceai and MTSplice are readily integrated into VEP and can be added to variant annotations.
MMSeqs
MMSeqs is a rapid multiple sequence alignment tool. It is several orders of magnitude faster than hmmer and jackhmmer with similar accuracy. Currently the web server is not available for use but you can still use mmseqs through colabfold (see above).
Expasy Tools
Expasy is hosted by Swill Bioinformatics Resource Portal. This is not a single tool but a large collection of small tools that can be use independently from one another. There are several tools for sequence, structure and small molecule analysis from similarity searches to simple molecular weight/isoelectric point calculation. Each tool has its own web interface with detailed documentation.
Alphafold3 Server
AlphaFold Server is a web-service that can generate highly accurate biomolecular structure predictions containing proteins, DNA, RNA, ligands, ions, and also model chemical modifications for proteins and nucleic acids in one platform. It’s powered by the newest AlphaFold 3 model. While AF3 is publicly available pending agreement to certain license conditions the server provides an easier to use alternative.
Chai1 Server
Chai1 is another protein, DNA, RNA, ligand structure prediction tool that is developed by Discoverly labs. Based on their technical reports it is as accurate as Alphafold3 in most instances and shows better perfromance on antibody-protein interactions. The model is available openly in github and there is a web interface for ease of use.
PhaSePred
Phase separation (PS) mediates the compartmentalization of proteins and nucleic acids in cell. This process is driven by multivalent weak interactions mediated by intrinsically disordered regions (IDRs) or multiple modular domains. A difference between these two interactions is that a single molecule species can undergo IDR-mediated phase separation, while phase separation mediated by multiple interacting domains often involves two or more different molecule species. PhaSePred is a centralized resource that provides self-assembling and partner-dependent phase-separating protein prediction and integrates scores from several PS-related predicting tools.
DeepLoc
DeepLoc 2.0 predicts the subcellular localization(s) of eukaryotic proteins. DeepLoc 2.0 is a multi-label predictor, which means that is able to predict one or more localizations for any given protein. It can differentiate between 10 different localizations: Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell membrane, Endoplasmic reticulum, Chloroplast, Golgi apparatus, Lysosome/Vacuole and Peroxisome. Additionally, DeepLoc 2.0 can predict the presence of the sorting signal(s) that had an influence on the prediction of the subcellular localization(s). One can use DeepLocPro for prokaryotic proteins and DeepLocRNA for RNA localization.
Phobius
Phobius is a tool that predicts the transmembrane topology and signal peptides of a protein from its amino acid sequence. It can identify membrane, signal peptide, or cytoplasmic loop states with a single label. It can also force the predictor to choose between two types of features to improve discrimination. Phobius is available for free local installation for academic use on Unix platforms with Perl version 5.6 or later. It can also be accessed through the Phobius web server.
ProtVar
ProtVar (Protein Variation) is a resource to investigate SNV missense variation (not InDels) in humans by presenting annotations which may be relevant to interpretation. The tool is similar to VEP. It is easier to use but not as robust as VEP (see above).