Predicting biophysical characteristics of proteins from their amino acid sequence
Most methods that predict per-residue characteristics from sequence are trained on information from in silico protein structures, which do not necessarily capture how the protein behaves in solution (e.g. helix fraying, loop movements). We are developing prediction approaches that are based on estimations of dynamics and conformation directly from experimental NMR data. These estimations are less accurate but can encompass the whole range of protein behaviour, from intrinsically disorded via molten globule to fully folded. This is the basis of the DynaMine method published at the end of 2013. We have evidence that the predictions add a new, physical, dimension to the protein sequence that has many uses, such as improving sequence alignment or detecting early folding events. We are continuing this work i) to define new biophysical features, ii) to investigate how these features change in evolution, iii) incorporate the effect of PTMs and iv) to relate this to conformational ambiguity (regions of proteins that are likely to change conformation under physiological conditions).
People
David Bickel
Postdoctoral researcher
Charlotte Crauwels
Ph.D. student
Adrian Diaz
Staff
Bhawna Dixit
Ph.D. student
Jose Gavaldá-GarcĂa
Ph.D. student
Sophie-Luise Heidig
Ph.D. student
Marina Margos
Internship student
Gabriele Orlando
Ph.D. student
Daniele Raimondi
Ph.D. student
Pathmanaban Ramasamy
Postdoctoral researcher
Joel Roca Martinez
Ph.D. student
Funding
G.0328.16N (Jan. 1, 2016-Dec. 31, 2019)
FoldMod - The role of local amino acid interactions in the folding of proteins, the stability of their fold and the location of post-translational modifications.
BB2B 2010-1-12 (Dec. 1, 2010-Nov. 30, 2015)
Brains Back to Brussels project - Combining experiment and informatics to study biopolymer dynamics and interactions.
RNAct (Jan. 1, 2019-Dec. 31, 2023)
The H2020-MSCA-ITN-2018 813239 <a href="http://rnact.eu/">RNAct project</a> focusses on 'Enabling proteins with RNA recognition motifs for synthetic biology and bio-analytics'.
ProteinContour (Jan. 1, 2021-Dec. 12, 2024)
In this project (FWO identifier G028821N), we combine mass spectrometry analysis expertise from UGent (CompOmics group, Lennart Martens) and UCL (Laurent Gatto) with our predictions to map the relationships between post-translational modifications, sub cellular location, interactions and biophysical features of proteins in human cells.
FWO-IRI ELIXIR (Jan. 1, 2023-Dec. 31, 2026)
Infrastructure grant from the Flemish government for <a href="https://www.elixir-belgium.org">ELIXIR-Belgium</a>, where we receive funding to develop services for the 2023-2026 period.
FWO-SB (Nov. 1, 2022-Oct. 31, 2026)
FWO-SB grant to Charlotte Crauwels to work on the design of hybrid GPCRs
Resources
DynaMine (Software tool, In-house)
Prediction of protein backbone dynamics from sequence only
EFoldMine (Software tool, In-house)
Prediction of protein early folding regions from sequence only
DisoMine (Software tool, In-house)
Prediction of protein disorder from sequence only
Start2Fold (Database, In-house)
Database with information on the early/intermediate/late folding regions of proteins, and their unfolding, from hydrogen/deuterium exchange data from NMR and X-ray crystallography
AmyPro (Database, External collaboration)
AmyPro is a database with information on aggregating regions of proteins.
RINspector (Software tool, External collaboration)
RINspector is a CytoScape app that combines protein-structure based network analysis with DynaMine predictions
PhyloCys (Software tool, In-house)
PhyloCys is a tool to predict cysteine disulphide bonding patterns in proteins from evolutionary sequence information.
Sephiroth (Software tool, In-house)
Sephiroth is a tool to predict the cysteine disulphide bonding pattern in proteins from evolutionary sequence information.
SeRenDIP (Software tool, External collaboration)
Sequence-based Homo- and Heteromeric Protein-protein Interaction sites prediction using Random Forest; a key feature of this method are the DynaMine predictions
DisProt 7.0 (Database, External collaboration)
DisProt is a database with annotations on disordered regions of proteins based on experimental observations.
MobiDB (Database, External collaboration)
MobiDB is a database of (predicted) annotations on protein disorder and mobility