software

The HECTOR software has been developed to design epitope-specific binders; by epitope-specific binders, we mean proteins that will bind specifically to a defined part of the target. This is a challenging problem, because it is difficult to find a complementary surface that will "dock" a defined epitope. To that end, the HECTOR approach builds on a novel surface fingerprinting method that can be used to describe the relationship between a surface and its ideally complementary binder. Such an fingerprint can be used for ultra-fast evaluation of surface complementarity and docking of molecular structures. It was specifically developed for parallel execution on modern graphics processors for maximum performance.

The HECTOR method has helped us to create novel binders against therapeutic targets with a high success rate.

Having designed proteins with complementary surfaces against defined epitopes using HECTOR, we would like to optimise the amino acids of the designed proteins.

It is difficult to computationally design a protein with even tens of amino acids because of the combinatoric explosion involved in evaluating the energy of all constituent amino acids in all possible conformations. To this end, we have developed SINAI. This software suggests an amino acid sequence, calculates the conformation energy of this sequence and evalulates the free energy of interaction between the proposed candidate protein and the target. This process is repeated to obtain the optimal structure(s). These calculations are performed efficiently and quickly, as parts of the calculation are tensorised. The whole method is based on the principles described previously (Maksymenko et al. (2023) Cell Reports Methods, 3, article no.100560).

Of course SINAI can also be used on its own to optimise the sequence of an already functional protein and to stabilise pre-existent protein-protein interactions.