Principal Computational Chemist

4 weeks ago

Cambridge, United Kingdom Amphista Therapeutics Limited Full time

Amphista Therapeutics is focused on transforming the lives of patients with severe diseases including cancer. The company is applying its proprietary Amphista degrader platform to advance new approaches in targeted protein degradation (TPD). They aim to address the challenges faced by earlier stage TPD research and to realise the full therapeutic potential of this transformational approach. Founded by Advent Life Sciences, Amphista is a spin-out of TPD expert Professor Alessio Ciulli’s laboratories at the University of Dundee. The Company has raised over $60M to date and is funded by leading life science investors including Forbion, Gilde Healthcare, Novartis Venture Fund, Advent Life Sciences, Eli Lilly & Company and The Dementia Discovery Fund. For more information, please visit: www.amphista.com



We are looking for an experienced Senior Principal Computational Chemist, with a keen interest in targeted protein degradation (TPD) and small molecule drug design, to join our growing Cheminformatics & Computational Chemistry team.


The Cheminformatics & Computational Chemistry team is a cross-functional team that applies their knowledge to the exciting, developing field of targeted protein degradation medicines. The role is to aid the advancement of our small molecule TPD programmes by devising computational solutions to project-specific challenges and applying new and existing technologies to support the needs of our wider portfolio.


As a Principal Computational Chemist, you will have a significant scientific leadership role within the team. You will utilise your extensive experience in computational chemistry, biomolecular structural analysis, and computational modelling techniques to advance our TPD drug programmes. You will work closely with fellow computational chemists, medicinal chemists, cheminformaticians and bioinformaticians, to develop data and modelling pipelines, identify and apply innovative technologies, and employ state of the art computer-aided drug design techniques.


Your contributions will directly impact multiple drug discovery projects, while also helping to grow the proprietary Amphista protein degrading platform. You will be a key part of the wider chemistry team and will work with scientific and project leaders from across the company, with high visibility to senior leadership including CSO, CEO and others.


Primary Responsibilities

·Lead the computational chemistry support for multiple TPD drug programmes, working closely with fellow computational chemists, medicinal chemists, informaticians, and the rest of the project team

·Gather, analyse, and report on biomolecular and ternary complex structural data to derive novel insights into SAR and TPD mechanisms, including the use of 3D ligand- and structure-based computational and physics-based modelling (e.g. molecular dynamics, water-site analysis, FEP, QM)


·Build, evaluate and deliver structure- and ligand-based models, e.g. pharmacophore, docking etc. to advance our TPD projects, and support their use by project teams


·Apply a wide range of computer-aided drug design techniques to design targeted protein degraders, including virtual screening, bioisosteric replacements, scaffold hopping and linker design, MMPA and de novo design


·Develop processes, customisable workflows and computational techniques that can be adapted and applied across our portfolio


·Work with the team to identify and develop innovative approaches to expand our computational chemistry capabilities, and contribute towards the long-term strategic thinking of the team


Additional Responsibilities

·Act as a key domain expert for computational chemistry and the handling of biomolecular data, and consult with scientific teams across Amphista


·Maintain a comprehensive awareness of contemporary literature developments in computational drug discovery and medicinal chemistry, with particular attention to targeted protein degradation and areas relevant to Amphista programmes


·Collaborate and communicate effectively with a variety of stakeholders, including chemists, structural biologists, bioinformaticians and biologists


·Nurture talent by supporting junior members of the team in their work, sharing your experience, and providing a mentoring role


·Clearly and effectively present plans and results internally, and at relevant external conferences and forums


·Undertake any other reasonable duties that may be allocated to the role


What’s on offer


  • Competitive salary
  • Flexible Benefits + core benefits Private Medical Insurance, Life Assurance at 4 x Salary, Critical Illness Cover and a Health Cash Plan
  • Discretionary Bonus Scheme
  • Allocation of Growth Shares
  • Pension scheme with 5% employer matched contribution
  • 25 days holiday + bank holidays
  • Holiday buy up to 10 days per year


More about Amphista


Amphista’s approaches use completely novel mechanisms to build on all the advantages of TPD while directly addressing the emerging limitations of existing TPD strategies to expand the utility of the field. We have shown our approach has the potential to be superior to all other TPD approaches (PROTACs, molecular glues etc) improved druglike properties and reduced tumour resistance potential. We have a range of projects in the discovery phase, initially focused on oncology with potential to expand into other therapy areas including CNS disease & immunology.


Initially founded from the laboratory of Professor Alessio Ciulli (University of Dundee) our team comprises both academic and drug discovery pioneers of the TPD field and a growing R&D team focused on advancing a portfolio of medicines to the clinic using our proprietary next generation TPD technologies. We are continuing to grow and are looking for a key hire to expand our screening and assay teams.


The Amphista team comprises highly experienced drug discovery and TPD experts across both biology and chemistry disciplines, creating the ideal learning environment to advance your scientific career development quickly. This is an exciting opportunity to join a fast growing and dynamic company operating at the cutting edge of protein degradation-based drug discovery to develop first-in-class medicines to treat cancer and other areas of high unmet medical need.

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