Drug development on a quantum computer
Diagnomics with its partner company, DNA-SEQ, offer an approach that is unique in the field of cancer genomics today. In addition to offering testing of the full functional genome, DNA SEQ will use the Patient Annotation™ tool of Diagnomics, Inc. and analytics of crystallographic experts to supply to patients and their physicians both detailed analysis of the mutated genes causing the patient’s cancer and possible drug therapies that may prove effective in combatting the cancer for the patient’s oncologist to consider and potentially prescribe.
In addition to bringing the specialized skillset of crystallography to bear, DNA SEQ has contracted with D-Wave Systems Inc. of Vancouver, British Columbia, to utilize D-Wave’s unique quantum computing capabilities in a joint research collaboration effort to significantly speed up the process of identifying effective protein kinase inhibitor molecules to cause the cessation of the rapid division of cells caused by cancerous mutations. Moreover, DNA SEQ will harness D-Wave’s quantum computing power to rapidly identify new small molecules to fight the relapse of cancer once initial first-in-line drugs begin to fail—which is a demonstrated phenomenon.
Analyzing the Human Kinome
DNA-SEQ combines innovations in the following areas to enrich our targeting mechanism:
- Machine Learning
- (Big Data) Cloud Computing
- Quantum Computing
The worldwide pursuit of a precise crystallography-based fight against cancer was initiated with the identification of the first crystal structure of a kinase - PKA. It remains the best characterization for the emerging structural language describing the context, or functional meaning, of any mutation in the largest family of proteins in nature. Furthermore, this structure also provides the best characterization of the “trigger” mechanism - the binding of ATP to the kinase and to the oncogenic kinases.
The 1ATP structure provides us with a picture of the "gun" ready to send the signal onto the oncogenic target. This singular event serves as the triggering mechanism (the Inception) of cancer. CML has been transformed into a chronic, manageable disease as a result of the characterization of the source of the oncogenic signal - ABL.
DNA-SEQ’s library of over 2,000 highly selected structures contains over 30 million XYZ coordinates. This library serves as testimony to the unprecedented worldwide tour de force of crystallography following the identification of that first structure. To date 16 drugs have received FDA approval and over 200 molecules are in clinical trials to test their veracity in competing with (inhibiting) the trigger mechanism of ATP.
This comprehensive library has been assembled in conjunction with our Alliance Partner, XTAL BioStructures, whose highly sophisticated crystallography expertise is also sought after by many pharmaceutical companies.
The major design criteria of the library was to enable us to align the structures with the trigger (the PKA with bound ATP), and to provide the full complement of critical metals and bound substrates. All other structures can than be aligned to that trigger. The alignment process is highly proprietary in that it involves numerous alterations (pruning) but it remains based on the first crystal structure - PKA.
The Intervention is accomplished by matching the crystal structure of inhibitor complexes to the activating mutation. And finally the Inhibition is accomplished by utilizing the crystal structure to match the inhibitor complexes with common resistance mutations.
DNA-SEQ’s Kinase Crystal Library is the organizing principle of the Alliance pipeline’s data gathering cycles. The data extracted from a patient’s DNA can then be modeled at the San Diego Super Computing Center and provided to the oncologist for a three dimensional visualization of the mutation.
With the modeling completed the search begins. DNA SEQ's crystal based "gene panels" provide precision screening for actionable genes based on crystallographic evidence. This is the critical step in which irrelevant mutants are discarded and a short list of structure based gene selection can be provided to the oncologist to determine their patients’ treatment plan.
Ultimately, DNA-SEQ’s Kinase Crystal Library will provide the aligned inhibitors for the quantum search algorithm being developed with D-Wave to more precisely match a molecule to a mutation. Efficacy is everything.